Emerging Roles of Macrophage Polarization in Osteoarthritis: Mechanisms and Therapeutic Strategies

Zimu Yuan, Decheng Jiang, Mengzhu Yang, Jie Tao, Xin Hu, Xiao Yang, Yi Zeng

PDF
Orthopaedic Surgery ›› 2024, Vol. 16 ›› Issue (3) : 532-550. DOI: 10.1111/os.13993
REVIEW ARTICLE

Emerging Roles of Macrophage Polarization in Osteoarthritis: Mechanisms and Therapeutic Strategies

Author information +
History +

Abstract

Osteoarthritis (OA) is the most common chronic degenerative joint disease in middle-aged and elderly people, characterized by joint pain and dysfunction. Macrophages are key players in OA pathology, and their activation state has been studied extensively. Various studies have suggested that macrophages might respond to stimuli in their microenvironment by changing their phenotypes to pro-inflammatory or anti-inflammatory phenotypes, which is called macrophage polarization. Macrophages accumulate and become polarized (M1 or M2) in many tissues, such as synovium, adipose tissue, bone marrow, and bone mesenchymal tissues in joints, while resident macrophages as well as other stromal cells, including fibroblasts, chondrocytes, and osteoblasts, form the joint and function as an integrated unit. In this study, we focus exclusively on synovial macrophages, adipose tissue macrophages, and osteoclasts, to investigate their roles in the development of OA. We review recent key findings related to macrophage polarization and OA, including pathogenesis, molecular pathways, and therapeutics. We summarize several signaling pathways in macrophage reprogramming related to OA, including NF-κB, MAPK, TGF-β, JAK/STAT, PI3K/Akt/mTOR, and NLRP3. Of note, despite the increasing availability of treatments for osteoarthritis, like intra-articular injections, surgery, and cellular therapy, the demand for more effective clinical therapies has remained steady. Therefore, we also describe the current prospective therapeutic methods that deem macrophage polarization to be a therapeutic target, including physical stimulus, chemical compounds, and biological molecules, to enhance cartilage repair and alleviate the progression of OA.

Keywords

Macrophage Polarization / Osteoarthritis / Signaling Pathway

Cite this article

Download citation ▾
Zimu Yuan, Decheng Jiang, Mengzhu Yang, Jie Tao, Xin Hu, Xiao Yang, Yi Zeng. Emerging Roles of Macrophage Polarization in Osteoarthritis: Mechanisms and Therapeutic Strategies. Orthopaedic Surgery, 2024, 16(3): 532‒550 https://doi.org/10.1111/os.13993

References

[1]
Katz JN, Arant KR, Loeser RF. Diagnosis and treatment of hip and knee osteoarthritis: a review. Jama. 2021;325(6):568–578.
[2]
Martel-Pelletier J, Barr AJ, Cicuttini FM, Conaghan PG, Cooper C, Goldring MB, et al. Osteoarthritis. Nat Rev Dis Primers. 2016;2:16072.
[3]
Allen KD, Thoma LM, Golightly YM. Epidemiology of osteoarthritis. Osteoarthr Cartil. 2022;30(2):184–195.
[4]
Tsezou A. Osteoarthritis year in review 2014: genetics and genomics. Osteoarthr Cartil. 2014;22(12):2017–2024.
[5]
Qiao L, Li Y, Sun S. Insulin exacerbates inflammation in fibroblast-like Synoviocytes. Inflammation. 2020;43(3):916–936.
[6]
Pan L, Xie W, Fu X, Lu W, Jin H, Lai J, et al. Inflammation and sarcopenia: a focus on circulating inflammatory cytokines. Exp Gerontol. 2021;154:111544.
[7]
Nedunchezhiyan U, Varughese I, Sun ARJ, Wu X, Crawford R, Prasadam I. Obesity, inflammation, and immune system in osteoarthritis. Front Immunol. 2022;13:907750.
[8]
Peshkova M, Lychagin A, Lipina M, di Matteo B, Anzillotti G, Ronzoni F, et al. Gender-related aspects in osteoarthritis development and progression: a review. Int J Mol Sci. 2022;23(5):2767.
[9]
Maly MR, Marriott KA, Chopp-Hurley JN. Osteoarthritis year in review 2019: rehabilitation and outcomes. Osteoarthr Cartil. 2020;28(3):249–266.
[10]
Driban JB, Harkey MS, Liu SH, Salzler M, McAlindon TE. Osteoarthritis and aging: young adults with osteoarthritis. Curr Epidemiol Rep. 2020;7(1):9–15.
[11]
Tardito S, Martinelli G, Soldano S, Paolino S, Pacini G, Patane M, et al. Macrophage M1/M2 polarization and rheumatoid arthritis: a systematic review. Autoimmun Rev. 2019;18(11):102397.
[12]
Jiao Y, Zhang T, Zhang C, Ji H, Tong X, Xia R, et al. Exosomal miR-30d-5p of neutrophils induces M1 macrophage polarization and primes macrophage pyroptosis in sepsis-related acute lung injury. Crit Care. 2021;25(1):356.
[13]
Wang C, Ma C, Gong L, Guo Y, Fu K, Zhang Y, et al. Macrophage polarization and its role in liver disease. Front Immunol. 2021;12:803037.
[14]
Boutilier AJ, Elsawa SF. Macrophage polarization states in the tumor microenvironment. Int J Mol Sci. 2021;22(13):6995.
[15]
Ginhoux F, Greter M, Leboeuf M, Nandi S, See P, Gokhan S, et al. Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science. 2010;330(6005):841–845.
[16]
Hashimoto D, Chow A, Noizat C, Teo P, Beasley MB, Leboeuf M, et al. Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes. Immunity. 2013;38(4):792–804.
[17]
Schulz C, Perdiguero EG, Chorro L, Szabo-Rogers H, Cagnard N, Kierdorf K, et al. A lineage of myeloid cells independent of Myb and hematopoietic stem cells. Science. 2012;336(6077):86–90.
[18]
Lavin Y, Mortha A, Rahman A, Merad M. Regulation of macrophage development and function in peripheral tissues. Nat Rev Immunol. 2015;15(12):731–744.
[19]
Culemann S, Grüneboom A, Nicolás-Ávila JÁ, Weidner D, Lämmle KF, Rothe T, et al. Locally renewing resident synovial macrophages provide a protective barrier for the joint. Nature. 2019;572(7771):670–675.
[20]
Udalova IA, Mantovani A, Feldmann M. Macrophage heterogeneity in the context of rheumatoid arthritis. Nat Rev Rheumatol. 2016;12(8):472–485.
[21]
Kraus VB, McDaniel G, Huebner JL, Stabler TV, Pieper CF, Shipes SW, et al. Direct in vivo evidence of activated macrophages in human osteoarthritis. Osteoarthr Cartil. 2016;24(9):1613–1621.
[22]
Wood MJ, Leckenby A, Reynolds G, Spiering R, Pratt AG, Rankin KS, et al. Macrophage proliferation distinguishes 2 subgroups of knee osteoarthritis patients. JCI Insight. 2019;4(2):e125325.
[23]
Krausgruber T, Blazek K, Smallie T, Alzabin S, Lockstone H, Sahgal N, et al. IRF5 promotes inflammatory macrophage polarization and TH1-TH17 responses. Nat Immunol. 2011;12(3):231–238.
[24]
Huang Z, Kraus VB. Does lipopolysaccharide-mediated inflammation have a role in OA? Nat Rev Rheumatol. 2016;12(2):123–129.
[25]
Murray PJ, Allen JE, Biswas SK, Fisher EA, Gilroy DW, Goerdt S, et al. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity. 2014;41(1):14–20.
[26]
Zhang H, Lin C, Zeng C, Wang Z, Wang H, Lu J, et al. Synovial macrophage M1 polarisation exacerbates experimental osteoarthritis partially through R-spondin-2. Ann Rheum Dis. 2018;77(10):1524–1534.
[27]
Fahy N, de Vries-van Melle ML, Lehmann J, Wei W, Grotenhuis N, Farrell E, et al. Human osteoarthritic synovium impacts chondrogenic differentiation of mesenchymal stem cells via macrophage polarisation state. Osteoarthr Cartil. 2014;22(8):1167–1175.
[28]
Haltmayer E, Ribitsch I, Gabner S, Rosser J, Gueltekin S, Peham J, et al. Co-culture of osteochondral explants and synovial membrane as in vitro model for osteoarthritis. PloS One. 2019;14(4):e0214709.
[29]
Manferdini C, Paolella F, Gabusi E, Silvestri Y, Gambari L, Cattini L, et al. From osteoarthritic synovium to synovial-derived cells characterization: synovial macrophages are key effector cells. Arthritis Res Ther. 2016;18:83.
[30]
Sun AR, Wu X, Liu B, Chen Y, Armitage CW, Kollipara A, et al. Pro-resolving lipid mediator ameliorates obesity induced osteoarthritis by regulating synovial macrophage polarisation. Sci Rep. 2019;9(1):426.
[31]
Sun AR, Panchal SK, Friis T, Sekar S, Crawford R, Brown L, et al. Obesity-associated metabolic syndrome spontaneously induces infiltration of pro-inflammatory macrophage in synovium and promotes osteoarthritis. PloS One. 2017;12(8):e0183693.
[32]
Wu CL, McNeill J, Goon K, Little D, Kimmerling K, Huebner J, et al. Conditional macrophage depletion increases inflammation and does not inhibit the development of osteoarthritis in obese macrophage Fas-induced apoptosis-transgenic mice. Arthritis Rheumatol. 2017;69(9):1772–1783.
[33]
Li L, Li Z, Li Y, Hu X, Zhang Y, Fan P. Profiling of inflammatory mediators in the synovial fluid related to pain in knee osteoarthritis. BMC Musculoskelet Disord. 2020;21(1):99.
[34]
Franzoni G, Mura L, Razzuoli E, de Ciucis CG, Fruscione F, Dell'Anno F, et al. Heterogeneity of phenotypic and functional changes to porcine monocyte-derived macrophages triggered by diverse polarizing factors in vitro. Int J Mol Sci. 2023;24(5):4308.
[35]
Shapouri-Moghaddam A, Mohammadian S, Vazini H, Taghadosi M, Esmaeili SA, Mardani F, et al. Macrophage plasticity, polarization, and function in health and disease. J Cell Physiol. 2018;233(9):6425–6440.
[36]
Zheng L, Wang Y, Qiu P, Xia C, Fang Y, Mei S, et al. Primary chondrocyte exosomes mediate osteoarthritis progression by regulating mitochondrion and immune reactivity. Nanomedicine (Lond). 2019;14(24):3193–3212.
[37]
Bailey KN, Furman BD, Zeitlin J, Kimmerling KA, Wu CL, Guilak F, et al. Intra-articular depletion of macrophages increases acute synovitis and alters macrophage polarity in the injured mouse knee. Osteoarthr Cartil. 2020;28(5):626–638.
[38]
Dakin SG, Coles M, Sherlock JP, Powrie F, Carr AJ, Buckley CD. Pathogenic stromal cells as therapeutic targets in joint inflammation. Nat Rev Rheumatol. 2018;14(12):714–726.
[39]
Sun Z, Liu Q, Lv Z, Li J, Xu X, Sun H, et al. Targeting macrophagic SHP2 for ameliorating osteoarthritis via TLR signaling. Acta Pharm Sin B. 2022;12(7):3073–3084.
[40]
Bondeson J, Blom AB, Wainwright S, Hughes C, Caterson B, van den Berg WB. The role of synovial macrophages and macrophage-produced mediators in driving inflammatory and destructive responses in osteoarthritis. Arthritis Rheum. 2010;62(3):647–657.
[41]
Blom AB, van Lent PL, Libregts S, Holthuysen AE, van der Kraan PM, van Rooijen N, et al. Crucial role of macrophages in matrix metalloproteinase-mediated cartilage destruction during experimental osteoarthritis: involvement of matrix metalloproteinase 3. Arthritis Rheum. 2007;56(1):147–157.
[42]
Wang D, Chai XQ, Hu SS, Pan F. Joint synovial macrophages as a potential target for intra-articular treatment of osteoarthritis-related pain. Osteoarthr Cartil. 2022;30(3):406–415.
[43]
Takano S, Uchida K, Miyagi M, Inoue G, Fujimaki H, Aikawa J, et al. Nerve growth factor regulation by TNF-α and IL-1β in synovial macrophages and fibroblasts in osteoarthritic mice. J Immunol Res. 2016;2016:5706359.
[44]
Kriegova E, Manukyan G, Mikulkova Z, Gabcova G, Kudelka M, Gajdos P, et al. Gender-related differences observed among immune cells in synovial fluid in knee osteoarthritis. Osteoarthr Cartil. 2018;26(9):1247–1256.
[45]
Kulkarni P, Srivastava V, Tootsi K, Electricwala A, Kharat A, Bhonde R, et al. Synovial fluid in knee osteoarthritis extends proinflammatory niche for macrophage polarization. Cell. 2022;11(24):4115.
[46]
Clockaerts S, Bastiaansen-Jenniskens YM, Runhaar J, van Osch GJVM, van Offel JF, Verhaar JAN, et al. The infrapatellar fat pad should be considered as an active osteoarthritic joint tissue: a narrative review. Osteoarthr Cartil. 2010;18(7):876–882.
[47]
Kouroupis D, Kaplan LD, Best TM. Human infrapatellar fat pad mesenchymal stem cells show immunomodulatory exosomal signatures. Sci Rep. 2022;12(1):3609.
[48]
Favero M, el-Hadi H, Belluzzi E, Granzotto M, Porzionato A, Sarasin G, et al. Infrapatellar fat pad features in osteoarthritis: a histopathological and molecular study. Rheumatology (Oxford). 2017;56(10):1784–1793.
[49]
Barboza E, Hudson J, Chang WP, Kovats S, Towner RA, Silasi-Mansat R, et al. Profibrotic infrapatellar fat pad remodeling without M1 macrophage polarization precedes knee osteoarthritis in mice with diet-induced obesity. Arthritis Rheumatol. 2017;69(6):1221–1232.
[50]
Davis JE, Ward RJ, MacKay JW, Lu B, Price LL, McAlindon TE, et al. Effusion-synovitis and infrapatellar fat pad signal intensity alteration differentiate accelerated knee osteoarthritis. Rheumatology (Oxford). 2019;58(3):418–426.
[51]
Wei W, Rudjito R, Fahy N, Bos KP, Verhaar JA, Clockaerts S, et al. The infrapatellar fat pad from diseased joints inhibits chondrogenesis of mesenchymal stem cells. Eur Cell Mater. 2015;30:303–314.
[52]
Da-Wa ZX, Jun M, Chao-Zheng L, Sen-Lin Y, Chuan L, De-Chun L, et al. Exosomes Derived from M2 macrophages exert a therapeutic effect via inhibition of the PI3K/AKT/mTOR pathway in rats with knee osteoarthritic. Biomed Res Int. 2021;2021:7218067.
[53]
Li P, Lv S, Jiang W, Si L, Liao B, Zhao G, et al. Exosomes derived from umbilical cord mesenchymal stem cells protect cartilage and regulate the polarization of macrophages in osteoarthritis. Ann Transl Med. 2022;10(18):976.
[54]
Wu J, Kuang L, Chen C, Yang J, Zeng WN, Li T, et al. miR-100-5p-abundant exosomes derived from infrapatellar fat pad MSCs protect articular cartilage and ameliorate gait abnormalities via inhibition of mTOR in osteoarthritis. Biomaterials. 2019;206:87–100.
[55]
Xu J, Ye Z, Han K, Zheng T, Zhang T, Dong S, et al. Infrapatellar fat pad mesenchymal stromal cell-derived exosomes accelerate tendon-bone healing and intra-articular graft remodeling after anterior cruciate ligament reconstruction. Am J Sports Med. 2022;50(3):662–673.
[56]
Chen Y, Wang T, Guan M, Zhao W, Leung FKL, Pan H, et al. Bone turnover and articular cartilage differences localized to subchondral cysts in knees with advanced osteoarthritis. Osteoarthr Cartil. 2015;23(12):2174–2183.
[57]
Day JS, Ding M, van der Linden JC, Hvid I, Sumner DR, Weinans H. A decreased subchondral trabecular bone tissue elastic modulus is associated with pre-arthritic cartilage damage. J Orthop Res. 2001;19(5):914–918.
[58]
Prieto-Potin I, Largo R, Roman-Blas JA, Herrero-Beaumont G, Walsh DA. Characterization of multinucleated giant cells in synovium and subchondral bone in knee osteoarthritis and rheumatoid arthritis. BMC Musculoskelet Disord. 2015;16:226.
[59]
Geurts J, Patel A, Hirschmann MT, Pagenstert GI, Müller-Gerbl M, Valderrabano V, et al. Elevated marrow inflammatory cells and osteoclasts in subchondral osteosclerosis in human knee osteoarthritis. J Orthop Res. 2016;34(2):262–269.
[60]
Li G, Yin J, Gao J, Cheng TS, Pavlos NJ, Zhang C, et al. Subchondral bone in osteoarthritis: insight into risk factors and microstructural changes. Arthritis Res Ther. 2013;15(6):223.
[61]
Su W, Liu G, Liu X, Zhou Y, Sun Q, Zhen G, et al. Angiogenesis stimulated by elevated PDGF-BB in subchondral bone contributes to osteoarthritis development. JCI Insight. 2020;5(8):e135446.
[62]
Jiang G, Li S, Yu K, He B, Hong J, Xu T, et al. A 3D-printed PRP-GelMA hydrogel promotes osteochondral regeneration through M2 macrophage polarization in a rabbit model. Acta Biomater. 2021;128:150–162.
[63]
Taniguchi K, Karin M. NF-kappaB, inflammation, immunity and cancer: coming of age. Nat Rev Immunol. 2018;18(5):309–324.
[64]
Zhang Q, Lenardo MJ, Baltimore D. 30 years of NF-kappaB: a blossoming of relevance to human pathobiology. Cell. 2017;168(1–2):37–57.
[65]
Sun SC. The non-canonical NF-kappaB pathway in immunity and inflammation. Nat Rev Immunol. 2017;17(9):545–558.
[66]
Capece D, Verzella D, Flati I, Arboretto P, Cornice J, Franzoso G. NF-kappaB: blending metabolism, immunity, and inflammation. Trends Immunol. 2022;43(9):757–775.
[67]
Napetschnig J, Wu H. Molecular basis of NF-kappaB signaling. Annu Rev Biophys. 2013;42:443–468.
[68]
Hayden MS, Ghosh S. Shared principles in NF-kappaB signaling. Cell. 2008;132(3):344–362.
[69]
Yu H, Lin L, Zhang Z, Zhang H, Hu H. Targeting NF-kappaB pathway for the therapy of diseases: mechanism and clinical study. Signal Transduct Target Ther. 2020;5(1):209.
[70]
Lee CH, Chiang CF, Kuo FC, Su SC, Huang CL, Liu JS, et al. High-molecular-weight hyaluronic acid inhibits IL-1β-induced synovial inflammation and macrophage polarization through the GRP78-NF-κB signaling pathway. Int J Mol Sci. 2021;22(21):12035.
[71]
Lu Y, Liu L, Pan J, Luo B, Zeng H, Shao Y, et al. MFG-E8 regulated by miR-99b-5p protects against osteoarthritis by targeting chondrocyte senescence and macrophage reprogramming via the NF-kappaB pathway. Cell Death Dis. 2021;12(6):533.
[72]
Jiang H, Zhang Y, Hu G, Shang X, Ming J, Deng M, et al. Innate/inflammatory bioregulation of surfactant protein D alleviates rat osteoarthritis by inhibiting toll-like receptor 4 signaling. Front Immunol. 2022;13:913901.
[73]
Gong J, Li J, Dong H, Chen G, Qin X, Hu M, et al. Inhibitory effects of berberine on proinflammatory M1 macrophage polarization through interfering with the interaction between TLR4 and MyD88. BMC Complement Altern Med. 2019;19(1):314.
[74]
Mo H, Wang Z, He Z, Wan J, Lu R, Wang C, et al. Decreased Peli1 expression attenuates osteoarthritis by protecting chondrocytes and inhibiting M1-polarization of macrophages. Bone Joint Res. 2023;12(2):121–132.
[75]
Barreto G, Senturk B, Colombo L, Brück O, Neidenbach P, Salzmann G, et al. Lumican is upregulated in osteoarthritis and contributes to TLR4-induced pro-inflammatory activation of cartilage degradation and macrophage polarization. Osteoarthr Cartil. 2020;28(1):92–101.
[76]
Musumeci G, Castrogiovanni P, Trovato F, Weinberg A, al-Wasiyah M, Alqahtani M, et al. Biomarkers of chondrocyte apoptosis and autophagy in osteoarthritis. Int J Mol Sci. 2015;16(9):20560–20575.
[77]
Li J, Ye F, Xu X, Xu P, Wang P, Zheng G, et al. Targeting macrophage M1 polarization suppression through PCAF inhibition alleviates autoimmune arthritis via synergistic NF-κB and H3K9Ac blockade. J Nanobiotechnol. 2023;21(1):280.
[78]
Yunna C, Mengru H, Lei W, Weidong C. Macrophage M1/M2 polarization. Eur J Pharmacol. 2020;877:173090.
[79]
Chung SW, Kang BY, Kim SH, Pak YK, Cho D, Trinchieri G, et al. Oxidized low density lipoprotein inhibits interleukin-12 production in lipopolysaccharide-activated mouse macrophages via direct interactions between peroxisome proliferator-activated receptor-gamma and nuclear factor-kappa B. J Biol Chem. 2000;275(42):32681–32687.
[80]
Hata A, Chen YG. TGF-beta signaling from receptors to Smads. Cold Spring Harb Perspect Biol. 2016;8(9):a022061.
[81]
Derynck R, Budi EH. Specificity, versatility, and control of TGF-beta family signaling. Sci Signal. 2019;12(570):eaav5183.
[82]
Chen G, Deng C, Li YP. TGF-beta and BMP signaling in osteoblast differentiation and bone formation. Int J Biol Sci. 2012;8(2):272–288.
[83]
Lamouille S, Xu J, Derynck R. Molecular mechanisms of epithelial-mesenchymal transition. Nat Rev Mol Cell Biol. 2014;15(3):178–196.
[84]
Yi JJ, Barnes AP, Hand R, Polleux F, Ehlers MD. TGF-beta signaling specifies axons during brain development. Cell. 2010;142(1):144–157.
[85]
Perez LG, Kempski J, McGee HM, Pelzcar P, Agalioti T, Giannou A, et al. TGF-beta signaling in Th17 cells promotes IL-22 production and colitis-associated colon cancer. Nat Commun. 2020;11(1):2608.
[86]
Itoh S, ten Dijke P. Negative regulation of TGF-beta receptor/Smad signal transduction. Curr Opin Cell Biol. 2007;19(2):176–184.
[87]
Li D, Zhang Q, Li L, Chen K, Yang J, Dixit D, et al. β2-microglobulin maintains glioblastoma stem cells and induces M2-like polarization of tumor-associated macrophages. Cancer Res. 2022;82(18):3321–3334.
[88]
Zhu X, Liang R, Lan T, Ding D, Huang S, Shao J, et al. Tumor-associated macrophage-specific CD155 contributes to M2-phenotype transition, immunosuppression, and tumor progression in colorectal cancer. J Immuno Ther Cancer. 2022;10(9):e004219.
[89]
Ma C, He D, Tian P, Wang Y, He Y, Wu Q, et al. miR-182 targeting reprograms tumor-associated macrophages and limits breast cancer progression. Proc Natl Acad Sci. 2022;119(6):e2114006119.
[90]
Dai M, Sui B, Xue Y, Liu X, Sun J. Cartilage repair in degenerative osteoarthritis mediated by squid type II collagen via immunomodulating activation of M2 macrophages, inhibiting apoptosis and hypertrophy of chondrocytes. Biomaterials. 2018;180:91–103.
[91]
Sun Y, Huang K, Mo L, Ahmad A, Wang D, Rong Z, et al. Eucommia ulmoides polysaccharides attenuate rabbit osteoarthritis by regulating the function of macrophages. Front Pharmacol. 2021;12:730557.
[92]
Lee H, Kim H, Seo J, Choi K, Lee Y, Park K, et al. TissueGene-C promotes an anti-inflammatory micro-environment in a rat monoiodoacetate model of osteoarthritis via polarization of M2 macrophages leading to pain relief and structural improvement. Inflammopharmacology. 2020;28(5):1237–1252.
[93]
Wang Q, Feng J, Tang L. Non-coding RNA related to MAPK signaling pathway in liver cancer. Int J Mol Sci. 2022;23(19):11908.
[94]
Fang JY, Richardson BC. The MAPK signalling pathways and colorectal cancer. Lancet Oncol. 2005;6(5):322–327.
[95]
Lee S, Rauch J, Kolch W. Targeting MAPK signaling in cancer: mechanisms of drug resistance and sensitivity. Int J Mol Sci. 2020;21(3):1102.
[96]
Asl ER, Amini M, Najafi S, Mansoori B, Mokhtarzadeh A, Mohammadi A, et al. Interplay between MAPK/ERK signaling pathway and MicroRNAs: a crucial mechanism regulating cancer cell metabolism and tumor progression. Life Sci. 2021;278:119499.
[97]
Hepworth EMW, Hinton SD. Pseudophosphatases as regulators of MAPK signaling. Int J Mol Sci. 2021;22(22):12595.
[98]
Zheng X, Jiang Q, Han M, Ye F, Wang M, Qiu Y, et al. FBXO38 regulates macrophage polarization to control the development of cancer and colitis. Cell Mol Immunol. 2023;20(11):1367–1378.
[99]
Qiu S, Xie L, Lu C, Gu C, Xia Y, Lv J, et al. Gastric cancer-derived exosomal miR-519a-3p promotes liver metastasis by inducing intrahepatic M2-like macrophage-mediated angiogenesis. J Exp Clin Cancer Res. 2022;41(1):296.
[100]
Moon SM, Lee SA, Han SH, Park BR, Choi MS, Kim JS, et al. Aqueous extract of Codium fragile alleviates osteoarthritis through the MAPK/NF-κB pathways in IL-1β-induced rat primary chondrocytes and a rat osteoarthritis model. Biomed Pharmacother. 2018;97:264–270.
[101]
Ran J, Ma C, Xu K, Xu L, He Y, Moqbel SAA, et al. Schisandrin B ameliorated chondrocytes inflammation and osteoarthritis via suppression of NF-κB and MAPK signal pathways. Drug Des Devel Ther. 2018;12:1195–1204.
[102]
Wu MH, Tsai CH, Huang YL, Fong YC, Tang CH. Visfatin promotes IL-6 and TNF-α production in human synovial fibroblasts by repressing miR-199a-5p through ERK, p38 and JNK signaling pathways. Int J Mol Sci. 2018;19(1):190.
[103]
Zhou F, Mei J, Han X, Li H, Yang S, Wang M, et al. Kinsenoside attenuates osteoarthritis by repolarizing macrophages through inactivating NF-κB/MAPK signaling and protecting chondrocytes. Acta Pharm Sin B. 2019;9(5):973–985.
[104]
Mahon OR, O'Hanlon S, Cunningham CC, McCarthy GM, Hobbs C, Nicolosi V, et al. Orthopaedic implant materials drive M1 macrophage polarization in a spleen tyrosine kinase- and mitogen-activated protein kinase-dependent manner. Acta Biomater. 2018;65:426–435.
[105]
Philips RL, Wang Y, Cheon HJ, Kanno Y, Gadina M, Sartorelli V, et al. The JAK-STAT pathway at 30: much learned, much more to do. Cell. 2022;185(21):3857–3876.
[106]
Tanaka Y, Luo Y, O'Shea JJ, Nakayamada S. Janus kinase-targeting therapies in rheumatology: a mechanisms-based approach. Nat Rev Rheumatol. 2022;18(3):133–145.
[107]
Hu X, li J, Fu M, Zhao X, Wang W. The JAK/STAT signaling pathway: from bench to clinic. Signal Transduct Target Ther. 2021;6(1):402.
[108]
Garcia S, Krausz S, Ambarus CA, Fernández BM, Hartkamp LM, van Es IE, et al. Tie2 signaling cooperates with TNF to promote the pro-inflammatory activation of human macrophages independently of macrophage functional phenotype. PloS One. 2014;9(1):e82088.
[109]
Wang Q, Zhou X, Yang L, Zhao Y, Chew Z, Xiao J, et al. The natural compound Notopterol binds and targets JAK2/3 to ameliorate inflammation and arthritis. Cell Rep. 2020;32(11):108158.
[110]
De Vries LCS, Duarte JM, De Krijger M, Welting O, Van Hamersveld PH, Van Leeuwen-Hilbers FW, et al. A JAK1 selective kinase inhibitor and tofacitinib affect macrophage activation and function. Inflamm Bowel Dis. 2019;25(4):647–660.
[111]
Xu J, Zhang J, Zhang Z, Gao Z, Qi Y, Qiu W, et al. Hypoxic glioma-derived exosomes promote M2-like macrophage polarization by enhancing autophagy induction. Cell Death Dis. 2021;12(4):373.
[112]
Xu M, Li X, Song L. Baicalin regulates macrophages polarization and alleviates myocardial ischaemia/reperfusion injury via inhibiting JAK/STAT pathway. Pharm Biol. 2020;58(1):655–663.
[113]
Liu Y, Wang L, Li S, Zhang T, Chen C, Hu J, et al. Mechanical stimulation improves rotator cuff tendon-bone healing via activating IL-4/JAK/STAT signaling pathway mediated macrophage M2 polarization. J Orthop Translat. 2022;37:78–88.
[114]
Degboe Y, Rauwel B, Baron M, Boyer JF, Ruyssen-Witrand A, Constantin A, et al. Polarization of rheumatoid macrophages by TNF targeting through an IL-10/STAT3 mechanism. Front Immunol. 2019;10:3.
[115]
Zhang MZ, Wang X, Wang Y, Niu A, Wang S, Zou C, et al. IL-4/IL-13-mediated polarization of renal macrophages/dendritic cells to an M2a phenotype is essential for recovery from acute kidney injury. Kidney Int. 2017;91(2):375–386.
[116]
Bhattacharjee A, Shukla M, Yakubenko VP, Mulya A, Kundu S, Cathcart MK. IL-4 and IL-13 employ discrete signaling pathways for target gene expression in alternatively activated monocytes/macrophages. Free Radic Biol Med. 2013;54:1–16.
[117]
Durham GA, Williams JJL, Nasim MT, Palmer TM. Targeting SOCS proteins to control JAK-STAT Signalling in disease. Trends Pharmacol Sci. 2019;40(5):298–308.
[118]
Liang YB, Tang H, Chen ZB, Zeng LJ, Wu JG, Yang W, et al. Downregulated SOCS1 expression activates the JAK1/STAT1 pathway and promotes polarization of macrophages into M1 type. Mol Med Rep. 2017;16(5):6405–6411.
[119]
Wang F, Zhang S, Vuckovic I, Jeon R, Lerman A, Folmes CD, et al. Glycolytic stimulation is not a requirement for M2 macrophage differentiation. Cell Metab. 2018;28(3):463–475.e4.
[120]
Ji L, Zhao X, Zhang B, Kang L, Song W, Zhao B, et al. Slc6a8-mediated creatine uptake and accumulation reprogram macrophage polarization via regulating cytokine responses. Immunity. 2019;51(2):272–284.e7.
[121]
Shan X, Hu P, Ni L, Shen L, Zhang Y, Ji Z, et al. Serine metabolism orchestrates macrophage polarization by regulating the IGF1-p38 axis. Cell Mol Immunol. 2022;19(11):1263–1278.
[122]
Latourte A, Cherifi C, Maillet J, Ea HK, Bouaziz W, Funck-Brentano T, et al. Systemic inhibition of IL-6/Stat3 signalling protects against experimental osteoarthritis. Ann Rheum Dis. 2017;76(4):748–755.
[123]
Zhou Q, Ren Q, Jiao L, Huang J, Yi J, Chen J, et al. The potential roles of JAK/STAT signaling in the progression of osteoarthritis. Front Endocrinol (Lausanne). 2022;13:1069057.
[124]
Hu Y, Gui Z, Zhou Y, Xia L, Lin K, Xu Y. Quercetin alleviates rat osteoarthritis by inhibiting inflammation and apoptosis of chondrocytes, modulating synovial macrophages polarization to M2 macrophages. Free Radic Biol Med. 2019;145:146–160.
[125]
Di-Luoffo M, Ben-Meriem Z, Lefebvre P, Delarue M, Guillermet-Guibert J. PI3K functions as a hub in mechanotransduction. Trends Biochem Sci. 2021;46(11):878–888.
[126]
Fruman DA, Chiu H, Hopkins BD, Bagrodia S, Cantley LC, Abraham RT. The PI3K pathway in human disease. Cell. 2017;170(4):605–635.
[127]
Yang J, Nie J, Ma X, Wei Y, Peng Y, Wei X. Targeting PI3K in cancer: mechanisms and advances in clinical trials. Mol Cancer. 2019;18(1):26.
[128]
Geraldo LH, Xu Y, Jacob L, Pibouin-Fragner L, Rao R, Maissa N, et al. SLIT2/ROBO signaling in tumor-associated microglia and macrophages drives glioblastoma immunosuppression and vascular dysmorphia. J Clin Invest. 2021;131(16):e141083.
[129]
Wang Y, Lyu Z, Qin Y, Wang X, Sun L, Zhang Y, et al. FOXO1 promotes tumor progression by increased M2 macrophage infiltration in esophageal squamous cell carcinoma. Theranostics. 2020;10(25):11535–11548.
[130]
Fu W, Hu W, Yi YS, Hettinghouse A, Sun G, Bi Y, et al. TNFR2/14-3-3ε signaling complex instructs macrophage plasticity in inflammation and autoimmunity. J Clin Invest. 2021;131(16):e144016.
[131]
Wu J, Zhang L, Shi J, He R, Yang W, Habtezion A, et al. Macrophage phenotypic switch orchestrates the inflammation and repair/regeneration following acute pancreatitis injury. EBioMedicine. 2020;58:102920.
[132]
Zhang H, Cai D, Bai X. Macrophages regulate the progression of osteoarthritis. Osteoarthr Cartil. 2020;28(5):555–561.
[133]
Sun K, Luo J, Guo J, Yao X, Jing X, Guo F. The PI3K/AKT/mTOR signaling pathway in osteoarthritis: a narrative review. Osteoarthr Cartil. 2020;28(4):400–409.
[134]
Liu X, Chen M, Luo J, Zhao H, Zhou X, Gu Q, et al. Immunopolarization-regulated 3D printed-electrospun fibrous scaffolds for bone regeneration. Biomaterials. 2021;276:121037.
[135]
Li K, Yan G, Huang H, Zheng M, Ma K, Cui X, et al. Anti-inflammatory and immunomodulatory effects of the extracellular vesicles derived from human umbilical cord mesenchymal stem cells on osteoarthritis via M2 macrophages. J Nanobiotechnology. 2022;20(1):38.
[136]
Zheng M, Zhu Y, Wei K, Pu H, Peng R, Xiao J, et al. Metformin attenuates the inflammatory response via the regulation of synovial M1 macrophage in osteoarthritis. Int J Mol Sci. 2023;24(6):5206.
[137]
Wang L, Hauenstein AV. The NLRP3 inflammasome: mechanism of action, role in disease and therapies. Mol Aspects Med. 2020;76:100889.
[138]
Mangan MSJ, Olhava EJ, Roush WR, Seidel HM, Glick GD, Latz E. Targeting the NLRP3 inflammasome in inflammatory diseases. Nat Rev Drug Discov. 2018;17(8):588–606.
[139]
Akbal A, Dernst A, Lovotti M, Mangan MSJ, McManus RM, Latz E. How location and cellular signaling combine to activate the NLRP3 inflammasome. Cell Mol Immunol. 2022;19(11):1201–1214.
[140]
Paik S, Kim JK, Silwal P, Sasakawa C, Jo EK. An update on the regulatory mechanisms of NLRP3 inflammasome activation. Cell Mol Immunol. 2021;18(5):1141–1160.
[141]
Swanson KV, Deng M, Ting JP. The NLRP3 inflammasome: molecular activation and regulation to therapeutics. Nat Rev Immunol. 2019;19(8):477–489.
[142]
Huang Y, Xu W, Zhou R. NLRP3 inflammasome activation and cell death. Cell Mol Immunol. 2021;18(9):2114–2127.
[143]
McAllister MJ, Chemaly M, Eakin AJ, Gibson DS, McGilligan VE. NLRP3 as a potentially novel biomarker for the management of osteoarthritis. Osteoarthr Cartil. 2018;26(5):612–619.
[144]
Wisitpongpun P, Potup P, Usuwanthim K. Oleamide-mediated polarization of M1 macrophages and IL-1beta production by regulating NLRP3-inflammasome activation in primary human monocyte-derived macrophages. Front Immunol. 2022;13:856296.
[145]
Liu T, Wang L, Liang P, Wang X, Liu Y, Cai J, et al. USP19 suppresses inflammation and promotes M2-like macrophage polarization by manipulating NLRP3 function via autophagy. Cell Mol Immunol. 2021;18(10):2431–2442.
[146]
Sun H, Sun Z, Xu X, Lv Z, Li J, Wu R, et al. Blocking TRPV4 ameliorates osteoarthritis by inhibiting M1 macrophage polarization via the ROS/NLRP3 signaling pathway. Antioxidants (Basel). 2022;11(12):2315.
[147]
Luo P, Peng S, Yan Y, Ji P, Xu J. IL-37 inhibits M1-like macrophage activation to ameliorate temporomandibular joint inflammation through the NLRP3 pathway. Rheumatology (Oxford). 2020;59(10):3070–3080.
[148]
Shen P, Jia S, Wang Y, Zhou X, Zhang D, Jin Z, et al. Mechanical stress protects against chondrocyte pyroptosis through lipoxin a(4) via synovial macrophage M2 subtype polarization in an osteoarthritis model. Biomed Pharmacother. 2022;153:113361.
[149]
Sun Y, Zuo Z, Kuang Y. An emerging target in the Battle against osteoarthritis: macrophage polarization. Int J Mol Sci. 2020;21(22):8513.
[150]
Ni L, Lin Z, Hu S, Shi Y, Jiang Z, Zhao J, et al. Itaconate attenuates osteoarthritis by inhibiting STING/NF-kappaB axis in chondrocytes and promoting M2 polarization in macrophages. Biochem Pharmacol. 2022;198:114935.
[151]
Khatab S, van Buul GM, Kops N, Bastiaansen-Jenniskens YM, Bos PK, Verhaar JA, et al. Intra-articular injections of platelet-Rich plasma Releasate reduce pain and synovial inflammation in a mouse model of osteoarthritis. Am J Sports Med. 2018;46(4):977–986.
[152]
Lu J, Zhang H, Pan J, Hu Z, Liu L, Liu Y, et al. Fargesin ameliorates osteoarthritis via macrophage reprogramming by downregulating MAPK and NF-kappaB pathways. Arthritis Res Ther. 2021;23(1):142.
[153]
Wang H, Zhang H, Fan K, Zhang D, Hu A, Zeng X, et al. Frugoside delays osteoarthritis progression via inhibiting miR-155-modulated synovial macrophage M1 polarization. Rheumatology (Oxford). 2021;60(10):4899–4909.
[154]
Zhang J, Rong Y, Luo C, Cui W. Bone marrow mesenchymal stem cell-derived exosomes prevent osteoarthritis by regulating synovial macrophage polarization. Aging (Albany NY). 2020;12(24):25138–25152.
[155]
Manferdini C, Paolella F, Gabusi E, Gambari L, Piacentini A, Filardo G, et al. Adipose stromal cells mediated switching of the pro-inflammatory profile of M1-like macrophages is facilitated by PGE2: in vitro evaluation. Osteoarthr Cartil. 2017;25(7):1161–1171.
[156]
Ma Y, Yang H, Zong X, Wu J, Ji X, Liu W, et al. Artificial M2 macrophages for disease-modifying osteoarthritis therapeutics. Biomaterials. 2021;274:120865.
[157]
Zhang L, Chen X, Cai P, Sun H, Shen S, Guo B, et al. Reprogramming mitochondrial metabolism in synovial macrophages of early osteoarthritis by a camouflaged meta-Defensome. Adv Mater. 2022;34(30):e2202715.
[158]
Zhou F, Mei J, Yang S, Han X, Li H, Yu Z, et al. Modified ZIF-8 nanoparticles attenuate osteoarthritis by reprogramming the metabolic pathway of synovial macrophages. ACS Appl Mater Interfaces. 2020;12(2):2009–2022.
[159]
Castorina S, Guglielmino C, Castrogiovanni P, Szychlinska MA, Ioppolo F, Massimino P, et al. Clinical evidence of traditional vs fast track recovery methodologies after total arthroplasty for osteoarthritic knee treatment. A retrospective observational study. Muscles Ligaments Tendons J. 2017;7(3):504–513.
[160]
Bull FC, al-Ansari SS, Biddle S, Borodulin K, Buman MP, Cardon G, et al. World Health Organization 2020 guidelines on physical activity and sedentary behaviour. Br J Sports Med. 2020;54(24):1451–1462.
[161]
Gill SD, McBurney H. Does exercise reduce pain and improve physical function before hip or knee replacement surgery? A systematic review and meta-analysis of randomized controlled trials. Arch Phys Med Rehabil. 2013;94(1):164–176.
[162]
Shan L, Shan B, Suzuki A, Nouh F, Saxena A. Intermediate and long-term quality of life after total knee replacement: a systematic review and meta-analysis. J Bone Joint Surg Am. 2015;97(2):156–168.
[163]
Silveira LS, Batatinha HAP, Castoldi A, Câmara NOS, Festuccia WT, Souza CO, et al. Exercise rescues the immune response fine-tuned impaired by peroxisome proliferator-activated receptors gamma deletion in macrophages. J Cell Physiol. 2019;234(4):5241–5251.
[164]
Abbasi J. Can exercise prevent knee osteoarthritis? Jama. 2017;318(22):2169–2171.
[165]
Emery CA, Pasanen K. Current trends in sport injury prevention. Best Pract Res Clin Rheumatol. 2019;33(1):3–15.
[166]
Liao B, Guan M, Tan Q, Wang G, Zhang R, Huang J, et al. Low-intensity pulsed ultrasound inhibits fibroblast-like synoviocyte proliferation and reduces synovial fibrosis by regulating Wnt/β-catenin signaling. J Orthop Translat. 2021;30:41–50.
[167]
Uddin SMZ, Komatsu DE. Therapeutic potential Low-intensity pulsed ultrasound for osteoarthritis: pre-clinical and clinical perspectives. Ultrasound Med Biol. 2020;46(4):909–920.
[168]
Xu Z, Li S, Wan L, Hu J, Lu H, Zhang T. Role of low-intensity pulsed ultrasound in regulating macrophage polarization to accelerate tendon-bone interface repair. J Orthop Res. 2022;41:919–929.
[169]
Letizia Mauro G, Scaturro D, Gimigliano F, Paoletta M, Liguori S, Toro G, et al. Physical agent modalities in early osteoarthritis: a scoping review. Medicina (Kaunas). 2021;57(11):1165.
[170]
Arden NK, Perry TA, Bannuru RR, Bruyère O, Cooper C, Haugen IK, et al. Non-surgical management of knee osteoarthritis: comparison of ESCEO and OARSI 2019 guidelines. Nat Rev Rheumatol. 2021;17(1):59–66.
[171]
Shu CC, Zaki S, Ravi V, Schiavinato A, Smith MM, Little CB. The relationship between synovial inflammation, structural pathology, and pain in post-traumatic osteoarthritis: differential effect of stem cell and hyaluronan treatment. Arthritis Res Ther. 2020;22(1):29.
[172]
Tarricone E, Mattiuzzo E, Belluzzi E, Elia R, Benetti A, Venerando R, et al. Anti-inflammatory performance of lactose-modified chitosan and hyaluronic acid mixtures in an in vitro macrophage-mediated inflammation osteoarthritis model. Cell. 2020;9(6):1328.
[173]
Jin L, Xu K, Liang Y, du P, Wan S, Jiang C. Effect of hyaluronic acid on cytokines and immune cells change in patients of knee osteoarthritis. BMC Musculoskelet Disord. 2022;23(1):812.
[174]
Rayahin JE, Buhrman JS, Zhang Y, Koh TJ, Gemeinhart RA. High and low molecular weight hyaluronic acid differentially influence macrophage activation. ACS Biomater Sci Eng. 2015;1(7):481–493.
[175]
Uçar D, Dıraçoğlu D, Süleyman T, Çapan N. Intra-articular hyaluronic acid as treatment in elderly and middle-aged patients with knee osteoarthritis. Open Rheumatol J. 2013;7:38–41.
[176]
Lohmander LS, Dalen N, Englund G, Hamalainen M, Jensen EM, Karlsson K, et al. Intra-articular hyaluronan injections in the treatment of osteoarthritis of the knee: a randomised, double blind, placebo controlled multicentre trial. Hyaluronan multicentre trial group. Ann Rheum Dis. 1996;55(7):424–431.
[177]
Perl A. Activation of mTOR (mechanistic target of rapamycin) in rheumatic diseases. Nat Rev Rheumatol. 2016;12(3):169–182.
[178]
Shan M, Qin J, Jin F, Han X, Guan H, Li X, et al. Autophagy suppresses isoprenaline-induced M2 macrophage polarization via the ROS/ERK and mTOR signaling pathway. Free Radic Biol Med. 2017;110:432–443.
[179]
Vergadi E, Ieronymaki E, Lyroni K, Vaporidi K, Tsatsanis C. Akt signaling pathway in macrophage activation and M1/M2 polarization. J Immunol. 2017;198(3):1006–1014.
[180]
Kang S, Nakanishi Y, Kioi Y, Okuzaki D, Kimura T, Takamatsu H, et al. Semaphorin 6D reverse signaling controls macrophage lipid metabolism and anti-inflammatory polarization. Nat Immunol. 2018;19(6):561–570.
[181]
Wu MM, Wang QM, Huang BY, Mai CT, Wang CL, Wang TT, et al. Dioscin ameliorates murine ulcerative colitis by regulating macrophage polarization. Pharmacol Res. 2021;172:105796.
[182]
Xu X, Gao W, Li L, Hao J, Yang B, Wang T, et al. Annexin A1 protects against cerebral ischemia-reperfusion injury by modulating microglia/macrophage polarization via FPR2/ALX-dependent AMPK-mTOR pathway. J Neuroinflammation. 2021;18(1):119.
[183]
Hooftman A, Angiari S, Hester S, Corcoran SE, Runtsch MC, Ling C, et al. The immunomodulatory metabolite itaconate modifies NLRP3 and inhibits inflammasome activation. Cell Metab. 2020;32(3):468–478 e7.
[184]
Mills EL, Ryan DG, Prag HA, Dikovskaya D, Menon D, Zaslona Z, et al. Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1. Nature. 2018;556(7699):113–117.
[185]
Muri J, Wolleb H, Broz P, Carreira EM, Kopf M. Electrophilic Nrf2 activators and itaconate inhibit inflammation at low dose and promote IL-1β production and inflammatory apoptosis at high dose. Redox Biol. 2020;36:101647.
[186]
Alonso-Pineiro JA, Gonzalez-Rovira A, Sánchez-Gomar I, Moreno JA, Durán-Ruiz MC. Nrf2 and heme Oxygenase-1 involvement in atherosclerosis related oxidative stress. Antioxidants (Basel). 2021;10(9):1463.
[187]
He R, Liu B, Xiong R, Geng B, Meng H, Lin W, et al. Itaconate inhibits ferroptosis of macrophage via Nrf2 pathways against sepsis-induced acute lung injury. Cell Death Discov. 2022;8(1):43.
[188]
Pan X, Shan H, Bai J, Gao T, Chen B, Shen Z, et al. Four-octyl itaconate improves osteoarthritis by enhancing autophagy in chondrocytes via PI3K/AKT/mTOR signalling pathway inhibition. Commun Biol. 2022;5(1):641.
[189]
Zhang P, Wang X, Peng Q, Jin Y, Shi G, Fan Z, et al. Four-octyl itaconate protects chondrocytes against H(2)O(2)-induced oxidative injury and attenuates osteoarthritis progression by activating Nrf2 signaling. Oxid Med Cell Longev. 2022;2022:2206167.
[190]
Zhang Q, Bai X, Wang R, Zhao H, Wang L, Liu J, et al. 4-octyl itaconate inhibits lipopolysaccharide (LPS)-induced osteoarthritis via activating Nrf2 signalling pathway. J Cell Mol Med. 2022;26(5):1515–1529.
[191]
Kon E, Engebretsen L, Verdonk P, Nehrer S, Filardo G. Clinical outcomes of knee osteoarthritis treated with an autologous protein solution injection: a 1-year pilot double-blinded randomized controlled trial. Am J Sports Med. 2018;46(1):171–180.
[192]
Everts P, Onishi K, Jayaram P, Lana JF, Mautner K. Platelet-Rich plasma: new performance understandings and therapeutic considerations in 2020. Int J Mol Sci. 2020;21(20):7794.
[193]
O'Donnell C, Migliore E, Grandi FC, Koltsov J, Lingampalli N, Cisar C, et al. Platelet-Rich plasma (PRP) from older males with knee osteoarthritis depresses chondrocyte metabolism and upregulates inflammation. J Orthop Res. 2019;37(8):1760–1770.
[194]
Uchiyama R, Toyoda E, Maehara M, Wasai S, Omura H, Watanabe M, et al. Effect of platelet-Rich plasma on M1/M2 macrophage polarization. Int J Mol Sci. 2021;22(5):2336.
[195]
Bennell KL, Hunter DJ, Paterson KL. Platelet-Rich plasma for the Management of hip and Knee Osteoarthritis. Curr Rheumatol Rep. 2017;19(5):24.
[196]
Zhang P, Li K, Kamali A, Ziadlou R, Ahmad P, Wang X, et al. Small molecules of herbal origin for osteoarthritis treatment: in vitro and in vivo evidence. Arthritis Res Ther. 2022;24(1):105.
[197]
Liu FC, Hung LF, Wu WL, Chang DM, Huang CY, Lai JH, et al. Chondroprotective effects and mechanisms of resveratrol in advanced glycation end products-stimulated chondrocytes. Arthritis Res Ther. 2010;12(5):R167.
[198]
Ma P, Yue L, Yang H, Fan Y, Bai J, Li S, et al. Chondroprotective and anti-inflammatory effects of amurensin H by regulating TLR4/Syk/NF-kappaB signals. J Cell Mol Med. 2020;24(2):1958–1968.
[199]
Wang Z, Huang J, Zhou S, Luo F, Xu W, Wang Q, et al. Anemonin attenuates osteoarthritis progression through inhibiting the activation of IL-1β/NF-κB pathway. J Cell Mol Med. 2017;21(12):3231–3243.
[200]
Zhang Y, Zeng Y. Curcumin reduces inflammation in knee osteoarthritis rats through blocking TLR4 /MyD88/NF-kappaB signal pathway. Drug Dev Res. 2019;80(3):353–359.
[201]
Yue B, Ren YJ, Zhang JJ, Luo XP, Yu ZL, Ren GY, et al. Anti-inflammatory effects of Fargesin on chemically induced inflammatory bowel disease in mice. Molecules. 2018;23(6):1380.
[202]
Xu X, Zhu R, Ying J, Zhao M, Wu X, Cao G, et al. Nephrotoxicity of herbal medicine and its prevention. Front Pharmacol. 2020;11:569551.
[203]
Yang M, Jiang L, Wang Q, Chen H, Xu G. Traditional Chinese medicine for knee osteoarthritis: An overview of systematic review. PloS One. 2017;12(12):e0189884.
[204]
Das P, Jana S, Kumar Nandi S. Biomaterial-based therapeutic approaches to osteoarthritis and cartilage repair through macrophage polarization. Chem Rec. 2022;22(9):e202200077.
[205]
Brown BN, Ratner BD, Goodman SB, Amar S, Badylak SF. Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine. Biomaterials. 2012;33(15):3792–3802.
[206]
Boersema GS, Grotenhuis N, Bayon Y, Lange JF, Bastiaansen-Jenniskens YM. The effect of biomaterials used for tissue regeneration purposes on polarization of macrophages. Biores Open Access. 2016;5(1):6–14.
[207]
Harrell CR, Markovic BS, Fellabaum C, Arsenijevic A, Volarevic V. Mesenchymal stem cell-based therapy of osteoarthritis: current knowledge and future perspectives. Biomed Pharmacother. 2019;109:2318–2326.
[208]
Liang X, Ding Y, Zhang Y, Tse HF, Lian Q. Paracrine mechanisms of mesenchymal stem cell-based therapy: current status and perspectives. Cell Transplant. 2014;23(9):1045–1059.
[209]
Chen W, Huang Y, Han J, Yu L, Li Y, Lu Z, et al. Immunomodulatory effects of mesenchymal stromal cells-derived exosome. Immunol Res. 2016;64(4):831–840.
[210]
Cosenza S, Ruiz M, Toupet K, Jorgensen C, Noël D. Mesenchymal stem cells derived exosomes and microparticles protect cartilage and bone from degradation in osteoarthritis. Sci Rep. 2017;7(1):16214.
[211]
Fernandes TL, Gomoll AH, Lattermann C, Hernandez AJ, Bueno DF, Amano MT. Macrophage: a potential target on cartilage regeneration. Front Immunol. 2020;11:111.
[212]
Munoz J, Akhavan NS, Mullins AP, Arjmandi BH. Macrophage polarization and osteoporosis: a review. Nutrients. 2020;12(10):2999.
[213]
Ruytinx P, Proost P, van Damme J, Struyf S. Chemokine-induced macrophage polarization in inflammatory conditions. Front Immunol. 2018;9:1930.
[214]
Liang C, Wu S, Xia G, Huang J, Wen Z, Zhang W, et al. Engineered M2a macrophages for the treatment of osteoarthritis. Front Immunol. 2022;13:1054938.
[215]
Wang Y, Li N, Zhang X, Horng T. Mitochondrial metabolism regulates macrophage biology. J Biol Chem. 2021;297(1):100904.
[216]
Jung SB, Choi MJ, Ryu D, Yi HS, Lee SE, Chang JY, et al. Reduced oxidative capacity in macrophages results in systemic insulin resistance. Nat Commun. 2018;9(1):1551.
[217]
Panahi Y, Alishiri GH, Parvin S, Sahebkar A. Mitigation of systemic oxidative stress by curcuminoids in osteoarthritis: results of a randomized controlled trial. J Diet Suppl. 2016;13(2):209–220.
[218]
Van den Bossche J, Baardman J, Otto NA, van der Velden S, Neele AE, van den Berg SM, et al. Mitochondrial dysfunction prevents repolarization of inflammatory macrophages. Cell Rep. 2016;17(3):684–696.
[219]
Yuan Y, Chen Y, Peng T, Li L, Zhu W, Liu F, et al. Mitochondrial ROS-induced lysosomal dysfunction impairs autophagic flux and contributes to M1 macrophage polarization in a diabetic condition. Clin Sci (Lond). 2019;133(15):1759–1777.
[220]
Mills CD, Kincaid K, Alt JM, Heilman MJ, Hill AM. M-1/M-2 macrophages and the Th1/Th2 paradigm. J Immunol. 2000;164(12):6166–6173.
[221]
Wynn TA, Chawla A, Pollard JW. Macrophage biology in development, homeostasis and disease. Nature. 2013;496(7446):445–455.
[222]
Rodríguez-Morales P, Franklin RA. Macrophage phenotypes and functions: resolving inflammation and restoring homeostasis. Trends Immunol. 2023;44(12):986–998.
[223]
Chistiakov DA, Bobryshev YV, Nikiforov NG, Elizova NV, Sobenin IA, Orekhov AN. Macrophage phenotypic plasticity in atherosclerosis: the associated features and the peculiarities of the expression of inflammatory genes. Int J Cardiol. 2015;184:436–445.
[224]
Liao S, Yang M, Li D, Wu Y, Sun H, Lu J, et al. Comprehensive bulk and single-cell transcriptome profiling give useful insights into the characteristics of osteoarthritis associated synovial macrophages. Front Immunol. 2022;13:1078414.
[225]
Liu Y, Lu T, Liu Z, Ning W, Li S, Chen Y, et al. Six macrophage-associated genes in synovium constitute a novel diagnostic signature for osteoarthritis. Front Immunol. 2022;13:936606.
[226]
Knights AJ, Farrell EC, Ellis OM, Song MJ, Appleton CT, Maerz T. Synovial macrophage diversity and activation of M-CSF signaling in post-traumatic osteoarthritis. bioRxiv; 2023.

RIGHTS & PERMISSIONS

2024 2024 The Authors. Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.
PDF

Accesses

Citations

Detail

Sections
Recommended

/