Targeted knockdown of PGAM5 in synovial macrophages efficiently alleviates osteoarthritis
- Yuhang Liu1,2, Ruihan Hao1,2, Jia Lv3, Jie Yuan4, Xuelei Wang5, Churong Xu6, Ding Ma1,2, Zhouyi Duan1,2, Bingjun Zhang1,2, Liming Dai1,2, Yiyun Cheng3, Wei Lu5, Xiaoling Zhang1,2
Author information
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1Department of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200092, China;
2National Facility for Translational Medicine, Shanghai 200240, China;
3Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, China;
4Department of Orthopaedic Surgery, The Second Hospital of Shanxi Medical University, Taiyuan 030001, China;
5CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai 200031, China;
6School of Medicine, Shanghai University, Shanghai 200444, China
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Received |
Revised |
Published |
06 Nov 2023 |
02 Jan 2024 |
10 Jul 2024 |
Issue Date |
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10 Jul 2024 |
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References
1. Coryell, P. R., Diekman, B. O.& Loeser, R. F. Mechanisms and therapeutic implications of cellular senescence in osteoarthritis. Nat. Rev. Rheumatol. 17, 47-57 (2021).
2. Loeser, R. F., Collins, J. A.& Diekman, B. O. Ageing and the pathogenesis of osteoarthritis. Nat. Rev. Rheumatol. 12, 412-420 (2016).
3. Conaghan, P. G.et al.Therapeutic options for targeting inflammatory osteoarthritis pain. Nat. Rev. Rheumatol. 15, 355-363 (2019).
4. Robinson, W. H.et al.Low-grade inflammation as a key mediator of the pathogenesis of osteoarthritis. Nat. Rev. Rheumatol. 12, 580-592 (2016).
5. Zhang, H.et al.Synovial macrophage M1 polarisation exacerbates experimental osteoarthritis partially through R-spondin-2. Ann. Rheum. Dis. 77, 1524-1534 (2018).
6. Dai, M.et al. Cartilage repair in degenerative osteoarthritis mediated by squid type II collagen via immunomodulating activation of M2 macrophages, inhibiting apoptosis and hypertrophy of chondrocytes. Biomaterials 180, 91-103 (2018).
7. Ma, Y.et al.Artificial M2 macrophages for disease-modifying osteoarthritis therapeutics. Biomaterials 274, 120865 (2021).
8. Lu, W.et al.Genetic deficiency of the mitochondrial protein PGAM5 causes a Parkinson's-like movement disorder. Nat. Commun. 5, 4930(2014).
9. Wang, Z.et al. The mitochondrial phosphatase PGAM5 functions at the convergence point of multiple necrotic death pathways. Cell 148, 228-243 (2012).
10. Ma, K.et al.Dynamic PGAM5 multimers dephosphorylate BCL-xL or FUNDC1 to regulate mitochondrial and cellular fate. Cell Death Differ. 27, 1036-1051 (2020).
11. Yu, B.et al.Mitochondrial phosphatase PGAM5 modulates cellular senescence by regulating mitochondrial dynamics. Nat. Commun. 11, 2549(2020).
12. Moriwaki, K.et al.The mitochondrial phosphatase PGAM5 is dispensable for necroptosis but promotes inflammasome activation in macrophages. J. Immunol. 196, 407-415 (2016).
13. Knights, A. J.et al.Synovial fibroblasts assume distinct functional identities and secrete R-spondin 2 in osteoarthritis. Ann. Rheum. Dis. 82, 272-282 (2023).
14. Sica A.& Mantovani, A. Macrophage plasticity and polarization: in vivo veritas. J. Clin. Investig. 122, 787-795 (2012).
15. Schaefer, L.et al.The matrix component biglycan is proinflammatory and signals through Toll-like receptors 4 and 2 in macrophages. J. Clin. Investig. 115, 2223-2233 (2005).
16. Yang, H.et al. MTORC1 coordinates the autophagy and apoptosis signaling in articular chondrocytes in osteoarthritic temporomandibular joint. Autophagy 16, 271-288 (2020).
17. Olefsky J. M.& Glass, C. K. Macrophages, inflammation, and insulin resistance. Annu. Rev. Physiol. 72, 219-246 (2010).
18. Guo, B.et al.Antagonism of PPAR-γ signaling expands human hematopoietic stem and progenitor cells by enhancing glycolysis. Nat. Med. 24, 360-367 (2018).
19. Li, J.et al.STAT6 contributes to renal fibrosis by modulating PPARα-mediated tubular fatty acid oxidation. Cell Death Dis. 13, 66(2022).
20. Rauschenberger, V.et al. The phosphatase Pgam5 antagonizes Wnt/β-Catenin signaling in embryonic anterior-posterior axis patterning. Development 144, 2234-2247 (2017).
21. Feng, Y.et al.Wnt/β-catenin-promoted macrophage alternative activation contributes to kidney fibrosis. J. Am. Soc. Nephrol. 29, 182-193 (2018).
22. Tian, X.et al.Long noncoding RNA LINC00662 promotes M2 macrophage polarization and hepatocellular carcinoma progression via activating Wnt/ β-catenin signaling. Mol. Oncol. 14, 462-483 (2020).
23. Oguma, K.et al.Activated macrophages promote Wnt signalling through tumour necrosis factor-alpha in gastric tumour cells. EMBO J. 27, 1671-1681 (2008).
24. Lu, Y.et al.lncRNA MIR100HG-derived miR-100 and miR-125b mediate cetuximab resistance via Wnt/β-catenin signaling. Nat. Med. 23, 1331-1341 (2017).
25. Fire, A.et al. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391, 806-811 (1998).
26. Evans C. H.Catering to chondrocytes. Sci. Transl. Med. 10, 469(2018).
27. Kazi, A.et al.GSK3 suppression upregulates β-catenin and c-Myc to abrogate KRas-dependent tumors. Nat. Commun. 9, 5154(2018).
28. Mahmoudian, A.et al.Early-stage symptomatic osteoarthritis of the knee - time for action. Nat. Rev. Rheumatol. 17, 621-632 (2021).
29. Wynn, T. A. & Vannella, K. M. Macrophages in tissue repair, regeneration,fibrosis. Immunity 44, 450-462 (2016).
30. Mantovani, A.et al.Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol. 23, 549-555 (2002).
31. Zhu, L.et al.TSC1 controls macrophage polarization to prevent inflammatory disease. Nat. Commun. 5, 4696(2014).
32. Lv, Z.et al.TRPV1 alleviates osteoarthritis by inhibiting M1 macrophage polarization via Ca2+/CaMKII/Nrf2 signaling pathway. Cell Death Dis. 12, 504(2021).
33. Zhang, Y.et al.Reprogramming of mitochondrial respiratory chain complex by targeting SIRT3-COX4I2 axis attenuates osteoarthritis progression. Adv. Sci. 10, e2206144(2023).
34. Vergadi, E.et al.Akt signaling pathway in macrophage activation and M1/M2 polarization. J. Immunol. 198, 1006-1014 (2017).
35. Zhao, S. J.et al. Macrophage MSR1 promotes BMSC osteogenic differentiation and M2-like polarization by activating PI3K/AKT/GSK3β/β-catenin pathway. Theranostics 10, 17-35 (2020).
36. Bode, J. G., Ehlting, C.& Häussinger, D. The macrophage response towards LPS and its control through the p38(MAPK)-STAT3 axis. Cell Signal. 24, 1185-1194 (2012).
37. Wang, L.et al. Gut microbial bile acid metabolite skews macrophage polarization and contributes to high-fat diet-induced colonic inflammation. Gut Microbes 12, 1-20 (2020).
38. Chen, J. Y.et al.CTRP9 induces macrophages polarization into M1 phenotype through activating JNK pathway and enhances VSMCs apoptosis in macrophages and VSMCs co-culture system. Exp. Cell Res. 395, 112194(2020).
39. Zhang, H., Cai, D.& Bai, X. Macrophages regulate the progression of osteoarthritis. Osteoarthr. Cartil. 28, 555-561 (2020).
40. Gao C.& Chen, Y. G. Dishevelled: the hub of Wnt signaling. Cell Signal. 22, 717-727 (2010).
41. Wu D.& Pan, W. GSK3: a multifaceted kinase in Wnt signaling. Trends Biochem. Sci. 35, 161-168 (2010).
42. Denk, D.et al. Expansion of T memory stem cells with superior anti-tumor immunity by Urolithin A-induced mitophagy. Immunity 55, 2059-2073.e8 (2022).
43. Bernkopf, D. B.et al.Pgam5 released from damaged mitochondria induces mitochondrial biogenesis via Wnt signaling. J. Cell Biol. 217, 1383-1394 (2018).
44. Lv, J.et al.Fluorination promotes the cytosolic delivery of genes, proteins, and peptides. Acc. Chem. Res. 55, 722-733 (2022).
45. Lv J.& Cheng, Y. Fluoropolymers in biomedical applications: state-of-the-art and future perspectives. Chem. Soc. Rev. 50, 5435-5467 (2021).
46. Cummings R. D.The mannose receptor ligands and the macrophage glycome. Curr. Opin. Struct. Biol. 75, 102394(2022).
47. Zhang, W.et al.Current research on pharmacologic and regenerative therapies for osteoarthritis. Bone Res. 4, 15040(2016).
48. Cao, W.et al.Tumor suppressor adenomatous polyposis coli sustains dendritic cell tolerance through IL-10 in a β-catenin-dependent manner. J. Immunol. 210, 1589-1597 (2023).
49. Wang, M.et al.A fluorinated dendrimer achieves excellent gene transfection efficacy at extremely low nitrogen to phosphorus ratios. Nat. Commun. 5, 3053(2014).
Funding
Yiyun Cheng (yycheng@mail.ustc.edu.cn) or Wei Lu (lvwei@sibs.ac.cn) or Xiaoling Zhang (xlzhang@shsmu.edu.cn)