Knowledge Mapping of Macrophages in Osteoporosis: A Bibliometric Analysis (1999–2023)

Abstract

Background: Osteoporosis is a common metabolic disorder that significantly impacts quality of life in the elderly population. Macrophages play a crucial role in the development of osteoporosis by regulating bone metabolism through cytokine secretion. However, there is a lack of scholarly literature in the field of bibliometrics on this topic.

Objective: This study provides a detailed analysis of the research focus and knowledge structure of macrophage studies in osteoporosis using bibliometrics.

Methods: The scientific literature on macrophage research in the context of osteoporosis, retrieved from the Web of Science Core Collection (WoSCC) database spanning from January 1999 to December 2023, has been incorporated for bibliometric examination. The data is methodically analyzed and visually represented using analytical and visualization tools including VOSviewer, CiteSpace, Scimago Graphica, the Bibliometrix R package, and Pajek.

Results and Conclusions: In the last quarter-century, there has been a consistent rise in the quantity of scholarly publications focusing on the relationship between macrophages and osteoporosis, resulting in a total of 1499 research documents. These studies have originated from 45 different countries, with China, South Korea, and the United States being the most prominent contributors, and the United States having the highest frequency of citations. Noteworthy research institutions involved in this field include Shanghai Jiao Tong University, Wonkwang University, Huazhong University of Science and Technology, and Seoul National University. The Journal of Bone and Mineral Research is widely regarded as the premier and most frequently referenced publication in the field. These publications involve the collaboration of 8744 authors, with Lee Myeung Su contributing the most articles, and Takayanagi being the most co-cited author. Key emerging research focal points are encapsulated in keywords such as “mTOR,” “BMSCs,” “bone regeneration,” and “exosome.” The relationships between exosome from macrophage sources and those from BMSCs, along with the regulatory role of the mTOR signaling pathway on macrophages, represent crucial directions for future development in this field. This study represents the inaugural comprehensive bibliometric analysis detailing trends and advancements in macrophage research within the osteoporosis domain. It delineates recent frontiers and hotspots, providing valuable insights for researchers in this particular area of study.

Keywords

Bibliometrics / Exosome / Macrophages / mTOR / Osteoporosis / VOSviewer / Web of Science (WoS)

References

[1] Aibar-AlmazáN A, Voltes-Martínez A, Castellote-Caballero Y, et al. Current status of the diagnosis and Management of Osteoporosis. Int J Mol Sci. 2022; 23(16): 9465.

[2] Xiao PL, Cui AY, Hsu CJ, Peng R, Jiang N, Xu XH, et al. Global, regional prevalence, and risk factors of osteoporosis according to the World Health Organization diagnostic criteria: a systematic review and meta-analysis. Osteoporos Int. 2022; 33(10): 2137–2153.

[3] Wang L, Yu W, Yin X, Cui L, Tang S, Jiang N, et al. Prevalence of osteoporosis and fracture in China: the China osteoporosis prevalence study. JAMA Netw Open. 2021; 4(8): e2121106.

[4] Clynes MA, Harvey NC, Curtis EM, Fuggle NR, Dennison EM, Cooper C. The epidemiology of osteoporosis. Br Med Bull. 2020; 133(1): 105–117.

[5] Willers C, Norton N, Harvey NC, Jacobson T, Johansson H, Lorentzon M, et al. Osteoporosis in Europe: a compendium of country-specific reports. Arch Osteoporos. 2022; 17(1): 23.

[6] Cummings SR, Melton LJ. Epidemiology and outcomes of osteoporotic fractures. Lancet. 2002; 359(9319): 1761–1767.

[7] Yang TL, Shen H, Liu A, Dong SS, Zhang L, Deng FY, et al. A road map for understanding molecular and genetic determinants of osteoporosis. Nat Rev Endocrinol. 2020; 16(2): 91–103.

[8] Yang DH, Yang MY. The role of macrophage in the pathogenesis of osteoporosis. Int J Mol Sci. 2019; 20(9): 2093.

[9] Dou C, Ding N, Zhao C, Hou T, Kang F, Cao Z, et al. Estrogen deficiency-mediated M2 macrophage osteoclastogenesis contributes to M1/M2 ratio alteration in ovariectomized osteoporotic mice. J Bone Miner Res. 2018; 33(5): 899–908.

[10] Yao Y, Cai X, Ren F, Ye Y, Wang F, Zheng C, et al. The macrophage-osteoclast axis in osteoimmunity and osteo-related diseases. Front Immunol. 2021; 12: 664871.

[11] Yang J, Park OJ, Kim J, Kwon Y, Yun CH, Han SH. Modulation of macrophage subtypes by IRF5 determines osteoclastogenic potential. J Cell Physiol. 2019; 234(12): 23033–23042.

[12] Horwood NJ. Macrophage polarization and bone formation: a review. Clin Rev Allergy Immunol. 2016; 51(1): 79–86.

[13] Muñoz J, Akhavan NS, Mullins AP, Arjmandi BH. Macrophage polarization and osteoporosis: a review. Nutrients. 2020; 12(10): 2999.

[14] Zhang X, Chen Q, Mao X. Magnesium enhances osteogenesis of BMSCs by tuning osteoimmunomodulation. Biomed Res Int. 2019; 2019: 7908205.

[15] Lu F, Wu X, Hu H, Zhang J, Song X, Jin X, et al. Yangonin treats inflammatory osteoporosis by inhibiting the secretion of inflammatory factors and RANKL expression. Inflammopharmacology. 2022; 30(4): 1445–1458.

[16] Komatsu N, Takayanagi H. Mechanisms of joint destruction in rheumatoid arthritis -immune cell-fibroblast-bone interactions. Nat Rev Rheumatol. 2022; 18(7): 415–429.

[17] Kokol P, BlaŽun Vošner H, Završnik J. Application of bibliometrics in medicine: a historical bibliometrics analysis. Health Info Libr J. 2021; 38(2): 125–138.

[18] Zhong D, Li Y, Huang Y, et al. Molecular mechanisms of exercise on cancer: a Bibliometrics study and visualization analysis via CiteSpace. Front Mol Biosci. 2021; 8: 797902.

[19] Lv J, Li Y, Shi S, Liu S, xu X, Wu H, et al. Frontier and hotspot evolution in Cardiorenal syndrome: a bibliometric analysis from 2003 to 2022. Curr Probl Cardiol. 2023; 48(8): 101238.

[20] Radu AF, Bungau SG, Negru PA, Marcu MF, Andronie-Cioara FL. In-depth bibliometric analysis and current scientific mapping research in the context of rheumatoid arthritis pharmacotherapy. Biomed Pharmacother. 2022; 154: 113614.

[21] Díaz-Faes AA, Bowman TD, Costas R. Towards a second generation of ‘social media metrics’: characterizing twitter communities of attention around science. PLoS One. 2019; 14(5): e0216408.

[22] Hassan-Montero Y, De-Moya-AnegóN F, Guerrero-Bote VP. SCImago Graphica: a new too for exploring and visually communicating data. Prof Inf. 2022; 31(5): 12.

[23] Batagelj V, Mrvar A. In: P Mutzel, M Junger, S Leipert, editors. Graph Drawing Pajek—Analysis and Visualization of Large Networks. Berlin: Springer-Verlag Berlin; 2002. p. 477–478.

[24] Chen CM, Song M. Visualizing a field of research: a methodology of systematic scientometric reviews. PLoS One. 2019; 14(10): 25.

[25] Aria M, Cuccurullo C. Bibliometrix: an R-tool for comprehensive science mapping analysis. J Informetr. 2017; 11(4): 959–975.

[26] Kwak HB, Kim JY, Kim KJ, Choi MK, Kim JJ, Kim KM, et al. Risedronate directly inhibits osteoclast differentiation and inflammatory bone loss. Biol Pharm Bull. 2009; 32(7): 1193–1198.

[27] Kwak HB, Kim HS, Lee MS, Kim KJ, Choi EY, Choi MK, et al. Pyridone 6, a pan-Janus-activated kinase inhibitor, suppresses osteoclast formation and bone resorption through down-regulation of receptor activator of nuclear factor-kappaB (NF-kappaB) ligand (RANKL)-induced c-Fos and nuclear factor of activated T cells (NFAT) c1 expression. Biol Pharm Bull. 2009; 32(1): 45–50.

[28] Irelli A, Sirufo MM, Scipioni T, de Pietro F, Pancotti A, Ginaldi L, et al. mTOR links tumor immunity and bone metabolism: what are the clinical implications? Int J Mol Sci. 2019; 20(23): 5841.

[29] Takayanagi H, Kim S, Matsuo K, Suzuki H, Suzuki T, Sato K, et al. Rankl maintains bone homeostasis through c-Fos-dependent induction of interferon-beta. Nature. 2002; 416(6882): 744–749.

[30] Koga T, Matsui Y, Asagiri M, Kodama T, de Crombrugghe B, Nakashima K, et al. Nfat and Osterix cooperatively regulate bone formation. Nat Med. 2005; 11(8): 880–885.

[31] Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature. 2003; 423(6937): 337–342.

[32] Teitelbaum SL. Bone resorption by osteoclasts. Science. 2000; 289(5484): 1504–1508.

[33] Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki SI, et al. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci U S A. 1998; 95(7): 3597–3602.

[34] Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, et al. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell. 1998; 93(2): 165–176.

[35] Kong YY, Yoshida H, Sarosi I, Tan HL, Timms E, Capparelli C, et al. Opgl is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature. 1999; 397(6717): 315–323.

[36] Takayanagi H. Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems. Nat Rev Immunol. 2007; 7(4): 292–304.

[37] Park JH, Lee NK, Lee SY. Current understanding of RANK signaling in osteoclast differentiation and maturation. Mol Cells. 2017; 40(10): 706–713.

[38] Lee K, Seo I, Choi MH, Jeong D. Roles of mitogen-activated protein kinases in osteoclast biology. Int J Mol Sci. 2018; 19(10): 3004.

[39] Loi F, Córdova LA, Zhang R, Pajarinen J, Lin TH, Goodman SB, et al. The effects of immunomodulation by macrophage subsets on osteogenesis in vitro. Stem Cell Res Ther. 2016; 7: 15.

[40] Liu K, Luo X, Lv ZY, et al. Macrophage-derived exosomes promote bone mesenchymal stem cells towards osteoblastic fate through microRNA-21a-5p. Front Bioeng Biotechnol. 2021; 9: 801432.

[41] Hou Y, Liu Y, Liang S, Ding R, Mo S, Yan D, et al. The novel target:exosoms derived from M2 macrophage. Int Rev Immunol. 2021; 40(3): 183–196.

[42] Liu J, Sun Z, You Y, Zhang L, Hou D, Gu G, et al. M2 macrophage-derived exosomal miR-486-5p influences the differentiation potential of bone marrow mesenchymal stem cells and osteoporosis. Aging. 2023; 15(18): 9499–9520.

[43] Xiong Y, Chen L, Yan C, Zhou W, Yu T, Sun Y, et al. M2 Macrophagy-derived exosomal miRNA-5106 induces bone mesenchymal stem cells towards osteoblastic fate by targeting salt-inducible kinase 2 and 3. J Nanobiotechnol. 2020; 18(1): 66.

[44] Ma T, Chen S, Wang J, Liang S, Chen M, Liu Q, et al. Enhanced osteolysis targeted therapy through fusion of exosomes derived from M2 macrophages and bone marrow mesenchymal stem cells: modulating macrophage polarization. Small. 2024; 20(7): e2303506.

[45] Yang M, Lu Y, Piao W, Jin H. The translational regulation in mTOR pathway. Biomolecules. 2022; 12(6): 802.

[46] Liu GY, Sabatini DM. mTOR at the nexus of nutrition, growth, ageing and disease. Nat Rev Mol Cell Biol. 2020; 21(4): 183–203.

[47] Zhang L, Guan Q, Wang Z, et al. Consequences of aging on bone. Aging Dis. 2023. doi:10.14336/AD.2023.1115

[48] Cheng W, Fu Y, Lin Z, et al. Lipoteichoic acid restrains macrophage senescence via β-catenin/FOXO1/REDD1 pathway in age-related osteoporosis. Aging Cell. 2024; 23(3): e14072.

[49] Hiraiwa M, Ozaki K, Yamada T, Iezaki T, Park G, Fukasawa K, et al. mTORC1 activation in osteoclasts prevents bone loss in a mouse model of osteoporosis. Front Pharmacol. 2019; 10: 684.

RIGHTS & PERMISSIONS

2024 The Author(s). Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.