Cellular senescence in cartilage and bone tissue aging: role in disease development and therapeutic potential

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

Cellular senescence induced by various types of stress leads to irreversible cell cycle arrest and alterations in gene expression, metabolism, chromatin organization, and activation of anti-apoptotic signaling pathways. This process results in the formation of a pro-inflammatory secretome, known as the senescence-associated secretory phenotype, which triggers chronic sterile inflammation (inflammaging).

This review summarizes current evidence on the role of cellular senescence in age-related changes and diseases of the joints and skeletal system, as well as potential therapeutic strategies.

Based on an articles search in the Google Scholar, PubMed (MEDLINE), Scopus, and Web of Science databases using specific keywords and their combinations and the AMSTAR 2 methodology, this review presents the role of cellular senescence in age-related changes and diseases of the joints and skeletal system. Data are presented demonstrating the presence of senescent cells with a senescence-associated secretory phenotype expressing the p16Ink4a protein in the microenvironment of cartilage and bone tissue. It was demonstrated that with advancing age, stem and progenitor cells, osteoblasts, osteocytes, and chondrocytes express senescence markers and acquire characteristic aging-associated traits such as genomic instability, telomere shortening, epigenetic modifications, proteostasis loss, and mitochondrial dysfunction. It has been demonstrated that cellular senescence and the development of the secretory phenotype are causally linked to chronic inflammation and contribute to the development of osteoporosis and osteoarthritis.

A new strategy for the treatment of osteoporosis and osteoarthritis—senotherapy—is presented, in which the therapeutic targets are senescent cells (senolytics) or various mechanisms responsible for their survival and transformation into the senescence-associated secretory phenotype (senomorphics).

Evidence shows that advances in senescence research over the past decade have laid the groundwork for novel therapeutic approaches targeting joint and bone diseases. Further investigation of the endocrine activity of senescence-associated secretory phenotype cartilage and bone cells is needed to provide the basis for understanding interactions among different systems of the aging organism and for developing strategies for the simultaneous treatment of age-related disorders.

About the authors

Natalia G. Plekhova

Pacific State Medical University

Author for correspondence.
Email: plekhova.ng@tgmu.ru
ORCID iD: 0000-0002-8701-7213
SPIN-code: 2685-9578

Dr. Sci. (Biology), Associate Professor

Russian Federation, Vladivostok

Polina A. Novikova

Pacific State Medical University

Email: vpo12345@mail.ru
ORCID iD: 0009-0002-5900-3938
Russian Federation, Vladivostok

Nikolay V. Tsvetov

Pacific State Medical University

Email: tsvetov0@gmail.com
ORCID iD: 0009-0009-0318-0661
Russian Federation, Vladivostok

References

  1. Li Z, Zhang Z, Ren Y, et al. Aging and age-related diseases: from mechanisms to therapeutic strategies. Biogerontology. 2021;22(2):165–187. doi: 10.1007/s10522-021-09910-5 EDN: ARCTCB
  2. Little-Letsinger SE, Rubin J, Diekman B, et al. Exercise to mend aged-tissue crosstalk in bone targeting osteoporosis & osteoarthritis. Semin Cell Dev Biol. 2022;123:22–35. doi: 10.1016/j.semcdb.2021.08.011 EDN: DDXNEL
  3. Föger-Samwald U, Kerschan-Schindl K, Butylina M, Pietschmann P. Age related osteoporosis: targeting cellular senescence. Int J Mol Sci. 2022;23(5):2701. doi: 10.3390/ijms23052701 EDN: NHERFT
  4. Coryell PR, Diekman BO, Loeser RF. Mechanisms and therapeutic implications of cellular senescence in osteoarthritis. Nat Rev Rheumatol. 2021;17(1):47–57. doi: 10.1038/s41584-020-00533-7 EDN: JUZZUZ
  5. Doolittle ML, Monroe DG, Farr JN, Khosla S. The role of senolytics in osteoporosis and other skeletal pathologies. Mech Ageing Dev. 2021;199:111565. doi: 10.1016/j.mad.2021.111565 EDN: KXFVBV
  6. López-Otín C, Blasco MA, Partridge L, et al. Hallmarks of aging: An expanding universe. Cell. 2023;186(2):243–278. doi: 10.1016/j.cell.2022.11.001 EDN: JTXISH
  7. de Magalhães JP. Cellular senescence in normal physiology. Science. 2024;384(6702):1300–1301. doi: 10.1126/science.adj7050 EDN: DMDQIN
  8. Gorgoulis V, Adams PD, Alimonti A, et al. Cellular senescence: defining a path forward. Cell. 2019;179(4):813–827. doi: 10.1016/j.cell.2019.10.005 EDN: PGJUED
  9. Suryadevara V, Hudgins AD, Rajesh A, et al. SenNet recommendations for detecting senescent cells in different tissues. Nat Rev Mol Cell Biol. 2024;25(12):1001–1023. doi: 10.1038/s41580-024-00738-8 EDN: MAAWKN
  10. Igrunkova АV, Valieva YМ, Kalinichenko АМ, et al. Cellular senescence: molecular biology and morphology. Molecular Medicine. 2022;20(4):16–21. doi: 10.29296/24999490-2022-04-03 EDN: EKRPQL
  11. Ishikawa F. Cellular senescence, an unpopular yet trustworthy tumor suppressor mechanism. Cancer Sci. 2003;94(11):944–947. doi: 10.1111/j.1349-7006.2003.tb01382.x
  12. Hall BM, Balan V, Gleiberman AS, et al. Aging of mice is associated with p16(Ink4a)- and β-galactosidase-positive macrophage accumulation that can be induced in young mice by senescent cells. Aging (Albany NY). 2016;8(7):1294–1315. doi: 10.18632/aging.100991 EDN: YDKCLM
  13. Blagosklonny MV. Cell senescence, rapamycin and hyperfunction theory of aging. Cell Cycle. 2022;21(14):1456–1467. doi: 10.1080/15384101.2022.2054636 EDN: UEAAGF
  14. Lawrence M, Goyal A, Pathak S, Ganguly P. Cellular senescence and inflammaging in the bone: pathways, genetics, anti-aging strategies and interventions. Int J Mol Sci. 2024;25(13):7411. doi: 10.3390/ijms25137411 EDN: XJQDWY
  15. Diekman BO, Loeser RF. Aging and the emerging role of cellular senescence in osteoarthritis. Osteoarthritis Cartilage. 2024;32(4):365–371. doi: 10.1016/j.joca.2023.11.018 EDN: TLCNFY
  16. Ravazzano L, Colaianni G, Tarakanova A, et al. Multiscale and multidisciplinary analysis of aging processes in bone. NPJ Aging. 2024;10(1):28. doi: 10.1038/s41514-024-00156-2 EDN: EUCFTW
  17. Plekhova NG, Krivolutskaya PA, Chernenko IN. Cellular mechanisms of age-dependent bone remodeling. Kazan Medical Journal. 2024;105(4):648–660. doi: 10.17816/KMJ632264 EDN: HFJNYE
  18. Chan CKF, Gulati GS, Sinha R, et al. Identification of the human skeletal stem cell. Cell. 2018;175(1):43–56.e21. doi: 10.1016/j.cell.2018.07.029 EDN: YJILHN
  19. Kikyo N. Circadian regulation of bone remodeling. Int J Mol Sci. 2024;25(9):4717. doi: 10.3390/ijms25094717 EDN: BEKOSC
  20. Teissier T, Temkin V, Pollak RD, Cox LS. Crosstalk between senescent bone cells and the bone tissue microenvironment influences bone fragility during chronological age and in diabetes. Front Physiol. 2022;13:812157. doi: 10.3389/fphys.2022.812157 EDN: PFCGBF
  21. Khosla S, Farr JN, Monroe DG. Cellular senescence and the skeleton: pathophysiology and therapeutic implications. J Clin Invest. 2022;132(3):e154888. doi: 10.1172/JCI154888 EDN: ITINYC
  22. van der Kraan PM, van den Berg WB. Chondrocyte hypertrophy and osteoarthritis: role in initiation and progression of cartilage degeneration? Osteoarthritis Cartilage. 2012;20(3):223–232. doi: 10.1016/j.joca.2011.12.003
  23. Mackie EJ, Ahmed YA, Tatarczuch L, et al. Endochondral ossification: how cartilage is converted into bone in the developing skeleton. Int J Biochem Cell Biol. 2008;40(1):46–62. doi: 10.1016/j.biocel.2007.06.009 EDN: MMSINB
  24. Jeon OH, David N, Campisi J, Elisseeff JH. Senescent cells and osteoarthritis: a painful connection. J Clin Invest. 2018;128(4):1229–1237. doi: 10.1172/JCI95147
  25. van Donkelaar CC, Wilson W. Mechanics of chondrocyte hypertrophy. Biomech Model Mechanobiol. 2012;11(5):655–664. doi: 10.1007/s10237-011-0340-0 EDN: PISQLL
  26. Li J, Dong S. The signaling pathways involved in chondrocyte differentiation and hypertrophic differentiation. Stem Cells Int. 2016;2016:2470351. doi: 10.1155/2016/2470351
  27. Rim YA, Nam Y, Ju JH. The role of chondrocyte hypertrophy and senescence in osteoarthritis initiation and progression. Int J Mol Sci. 2020;21(7):2358. doi: 10.3390/ijms21072358 EDN: GHPPWU
  28. Chen H, Tu M, Liu S, et al. Dendrobine alleviates cellular senescence and osteoarthritis via the ROS/NF-κB axis. Int J Mol Sci. 2023;24(3):2365. doi: 10.3390/ijms24032365 EDN: GTUYLC
  29. Xie J, Wang Y, Lu L, et al. Cellular senescence in knee osteoarthritis: molecular mechanisms and therapeutic implications. Ageing Res Rev. 2021;70:101413. doi: 10.1016/j.arr.2021.101413 EDN: FWQMLJ
  30. Ashraf S, Cha BH, Kim JS, et al. Regulation of senescence associated signaling mechanisms in chondrocytes for cartilage tissue regeneration. Osteoarthritis Cartilage. 2016;24(2):196–205. doi: 10.1016/j.joca.2015.07.008
  31. Yang X, Liu TC, Liu S, et al. Promoted viability and differentiated phenotype of cultured chondrocytes with low level laser irradiation potentiate efficacious cells for therapeutics. Front Bioeng Biotechnol. 2020;8:468. doi: 10.3389/fbioe.2020.00468 EDN: PVEDYG
  32. Solovyova IA, Demko IV, Sobko EA, et al. The role of p38 mapk in the development of immune inflammation. Bulletin Physiology and Pathology of Respiration. 2013;(49):105–114. EDN: RBQOLZ
  33. Del Rey MJ, Valín Á, Usategui A, et al. Senescent synovial fibroblasts accumulate prematurely in rheumatoid arthritis tissues and display an enhanced inflammatory phenotype. Immun Ageing. 2019;16:29. doi: 10.1186/s12979-019-0169-4 EDN: WLVXSJ
  34. Entz L, Falgayrac G, Chauveau C, et al. The extracellular matrix of human bone marrow adipocytes and glucose concentration differentially alter mineralization quality without impairing osteoblastogenesis. Bone Rep. 2022;17:101622. doi: 10.1016/j.bonr.2022.101622 EDN: PRBVAD
  35. Buettmann EG, Goldscheitter GM, Hoppock GA, et al. Similarities between disuse and age-induced bone loss. J Bone Miner Res. 2022;37(8):1417–1434. doi: 10.1002/jbmr.4643 EDN: HUGCFX
  36. Guerra RM, Fowler VM, Wang L. Osteocyte dendrites: how do they grow, mature, and degenerate in mineralized bone? Cytoskeleton (Hoboken). 2025;82(9):556–570. doi: 10.1002/cm.21964 EDN: VPQJSN
  37. Elnunu IS, Redmond JN, Obata Y, et al. Increased AGE cross-linking reduces the mechanical properties of osteons. JOM (1989). 2024;76(10):5692–5702. doi: 10.1007/s11837-024-06716-x EDN: TFPLOV
  38. Farr JN, Khosla S. Cellular senescence in bone. Bone. 2019;121:121–133. doi: 10.1016/j.bone.2019.01.015
  39. Wan M, Gray-Gaillard EF, Elisseeff JH. Cellular senescence in musculoskeletal homeostasis, diseases, and regeneration. Bone Res. 2021;9(1):41. doi: 10.1038/s41413-021-00164-y EDN: DKAUEC
  40. Fang CL, Liu B, Wan M. “Bone-SASP” in skeletal aging. Calcif Tissue Int. 2023;113(1):68–82. doi: 10.1007/s00223-023-01100-4 EDN: NZHGPK
  41. Kim HN, Xiong J, MacLeod RS, et al. Osteocyte RANKL is required for cortical bone loss with age and is induced by senescence. JCI Insight. 2020;5(19):e138815. doi: 10.1172/jci.insight.138815 EDN: IYYAQY
  42. Cui J, Shibata Y, Zhu T, et al. Osteocytes in bone aging: Advances, challenges, and future perspectives. Ageing Res Rev. 2022;77:101608. doi: 10.1016/j.arr.2022.101608 EDN: IPPGQA
  43. Wölfel EM, Fernandez-Guerra P, Nørgård MØ, et al. Senescence of skeletal stem cells and their contribution to age-related bone loss. Mech Ageing Dev. 2024;221:111976. doi: 10.1016/j.mad.2024.111976 EDN: XSPIOG
  44. Wang T, Huang S, He C. Senescent cells: A therapeutic target for osteoporosis. Cell Prolif. 2022;55(12):e13323. doi: 10.1111/cpr.13323
  45. Kurenkova AD, Medvedeva EV, Newton PT, Chagin AS. Niches for skeletal stem cells of mesenchymal origin. Front Cell Dev Biol. 2020;8:592. doi: 10.3389/fcell.2020.00592 EDN: JMQCSB
  46. Matsushita Y, Ono W, Ono N. Skeletal stem cells for bone development and repair: diversity matters. Curr Osteoporos Rep. 2020;18(3):189–198. doi: 10.1007/s11914-020-00572-9 EDN: QWVSPM
  47. Buck HV, Stains JP. Osteocyte-mediated mechanical response controls osteoblast differentiation and function. Front Physiol. 2024;15:1364694. doi: 10.3389/fphys.2024.1364694 EDN: ZCHJAN
  48. Pignolo RJ, Law SF, Chandra A. Bone aging, cellular senescence, and osteoporosis. JBMR Plus. 2021;5(4):e10488. doi: 10.1002/jbm4.10488 EDN: MCCWGP
  49. Melis S, Trompet D, Chagin AS, Maes C. Skeletal stem and progenitor cells in bone physiology, ageing and disease. Nat Rev Endocrinol. 2025;21(3):135–153. doi: 10.1038/s41574-024-01039-y EDN: VNCUVS
  50. Gharpinde MR, Pundkar A, Shrivastava S, et al. A comprehensive review of platelet-rich plasma and its emerging role in accelerating bone healing. Cureus. 2024;16(2):e54122. doi: 10.7759/cureus.54122 EDN: LYWFQA
  51. Spencer JA, Ferraro F, Roussakis E, et al. Direct measurement of local oxygen concentration in the bone marrow of live animals. Nature. 2014;508(7495):269–273. doi: 10.1038/nature13034 EDN: WQZGYB
  52. Guo B, Huang X, Chen Y, Broxmeyer HE. Ex vivo expansion and homing of human cord blood hematopoietic stem cells. Adv Exp Med Biol. 2023;1442:85–104. doi: 10.1007/978-981-99-7471-9_6
  53. Han L, Wang B, Wang R, et al. The shift in the balance between osteoblastogenesis and adipogenesis of mesenchymal stem cells mediated by glucocorticoid receptor. Stem Cell Res Ther. 2019;10(1):377. doi: 10.1186/s13287-019-1498-0 EDN: ADRHCG
  54. Solidum JGN, Jeong Y, Heralde F 3rd, Park D. Differential regulation of skeletal stem/progenitor cells in distinct skeletal compartments. Front Physiol. 2023;14:1137063. doi: 10.3389/fphys.2023.1137063
  55. Pioli PD, Casero D, Montecino-Rodriguez E, et al. Plasma cells are obligate effectors of enhanced myelopoiesis in aging bone marrow. Immunity. 2019;51(2):351–366.e6. doi: 10.1016/j.immuni.2019.06.006
  56. Olivieri F, Prattichizzo F, Grillari J, Balistreri CR. Cellular senescence and inflammaging in age-related diseases. Mediators Inflamm. 2018;2018:9076485. doi: 10.1155/2018/9076485
  57. Ma Y, Qi M, An Y, et al. Autophagy controls mesenchymal stem cell properties and senescence during bone aging. Aging Cell. 2018;17(1):e12709. doi: 10.1111/acel.12709
  58. Remark LH, Leclerc K, Ramsukh M, et al. Loss of Notch signaling in skeletal stem cells enhances bone formation with aging. Bone Res. 2023;11(1):50. doi: 10.1038/s41413-023-00283-8 EDN: YIFQUQ
  59. Saul D, Kosinsky RL, Atkinson EJ, et al. A new gene set identifies senescent cells and predicts senescence-associated pathways across tissues. Nat Commun. 2022;13(1):4827. doi: 10.1038/s41467-022-32552-1 EDN: OCEODX
  60. Hsu B, Cumming RG, Seibel MJ, et al. Reproductive hormones and longitudinal change in bone mineral density and incident fracture risk in older men: the concord health and aging in men project. J Bone Miner Res. 2015;30(9):1701–1708. doi: 10.1002/jbmr.2493
  61. Ganguly P, El-Jawhari JJ, Giannoudis PV, et al. Age-related changes in bone marrow mesenchymal stromal cells: a potential impact on osteoporosis and osteoarthritis development. Cell Transplant. 2017;26(9):1520–1529. doi: 10.1177/0963689717721201
  62. Wolock SL, Krishnan I, Tenen DE, et al. Mapping distinct bone marrow niche populations and their differentiation paths. Cell Rep. 2019;28(2):302–311.e5. doi: 10.1016/j.celrep.2019.06.031 EDN: KTSVWV
  63. Mitroulis I, Kalafati L, Bornhäuser M, et al. Regulation of the bone marrow niche by inflammation. Front Immunol. 2020;11:1540. doi: 10.3389/fimmu.2020.01540 EDN: LQEVXM
  64. Tuckermann J, Adams RH. The endothelium-bone axis in development, homeostasis and bone and joint disease. Nat Rev Rheumatol. 2021;17(10):608–620. doi: 10.1038/s41584-021-00682-3 EDN: VISCNT
  65. Vun J, Iqbal N, Jones E, Ganguly P. Anti-aging potential of platelet rich plasma (PRP): evidence from osteoarthritis (OA) and applications in senescence and inflammaging. Bioengineering (Basel). 2023;10(8):987. doi: 10.3390/bioengineering10080987 EDN: OEHJNZ
  66. Ferrucci L, Fabbri E. Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty. Nat Rev Cardiol. 2018;15(9):505–522. doi: 10.1038/s41569-018-0064-2 EDN: YIFCDZ
  67. Robbins PD, Jurk D, Khosla S, et al. Senolytic drugs: reducing senescent cell viability to extend health span. Annu Rev Pharmacol Toxicol. 2021;61:779–803. doi: 10.1146/annurev-pharmtox-050120-105018 EDN: FBNGDR
  68. Hay E, Bouaziz W, Funck-Brentano T, Cohen-Solal M. Sclerostin and bone aging: a mini-review. Gerontology. 2016;62(6):618–623. doi: 10.1159/000446278
  69. Gao Y, Patil S, Jia J. The development of molecular biology of osteoporosis. Int J Mol Sci. 2021;22(15):8182. doi: 10.3390/ijms22158182 EDN: CDXDCW
  70. Falvino A, Gasperini B, Cariati I, et al. Cellular senescence: the driving force of musculoskeletal diseases. Biomedicines. 2024;12(9):1948. doi: 10.3390/biomedicines12091948 EDN: NEKJUI
  71. Yao Z, Murali B, Ren Q, et al. Therapy-induced senescence drives bone loss. Cancer Res. 2020;80(5):1171–1182. doi: 10.1158/0008-5472.CAN-19-2348 EDN: PYMFRC
  72. Xu P, Lin B, Deng X, et al. VDR activation attenuates osteoblastic ferroptosis and senescence by stimulating the Nrf2/GPX4 pathway in age-related osteoporosis. Free Radic Biol Med. 2022;193(Pt 2):720–735. doi: 10.1016/j.freeradbiomed.2022.11.013 EDN: LBPPQV
  73. Guo Y, Jia X, Cui Y, et al. Sirt3-mediated mitophagy regulates AGEs-induced BMSCs senescence and senile osteoporosis. Redox Biol. 2021;41:101915. doi: 10.1016/j.redox.2021.101915 EDN: KYWCGO
  74. Li CJ, Xiao Y, Sun YC, et al. Senescent immune cells release grancalcin to promote skeletal aging. Cell Metab. 2022;34(1):184–185. doi: 10.1016/j.cmet.2021.12.003 EDN: JAJPKZ
  75. Schmauck-Medina T, Molière A, Lautrup S, et al. New hallmarks of ageing: a 2022 Copenhagen ageing meeting summary. Aging (Albany NY). 2022;14(16):6829–6839. doi: 10.18632/aging.204248 EDN: QVWBBH
  76. Yu H, Yao S, Zhou C, et al. Morroniside attenuates apoptosis and pyroptosis of chondrocytes and ameliorates osteoarthritic development by inhibiting NF-κB signaling. J Ethnopharmacol. 2021;266:113447. doi: 10.1016/j.jep.2020.113447 EDN: VPQUVI
  77. Tong L, Yu H, Huang X, et al. Current understanding of osteoarthritis pathogenesis and relevant new approaches. Bone Res. 2022;10(1):60. doi: 10.1038/s41413-022-00226-9 EDN: AJEAGA
  78. Kabalyk MA. Biomarkers of subchondral bone remodeling in osteoarthritis. Pacific Medical Journal. 2017;(1):36–41. doi: 10.17238/PmJ1609-1175.2017.1.37-41 EDN: VYOCGX
  79. Song C, Zhou Y, Cheng K, et al. Cellular senescence — Molecular mechanisms of intervertebral disc degeneration from an immune perspective. Biomed Pharmacother. 2023;162:114711. doi: 10.1016/j.biopha.2023.114711 EDN: XENXIF
  80. Zhang L, Xing R, Huang Z, et al. Inhibition of synovial macrophage pyroptosis alleviates synovitis and fibrosis in knee osteoarthritis. Mediators Inflamm. 2019;2019:2165918. doi: 10.1155/2019/2165918
  81. Chen B, Wang L, Xie D, Wang Y. Exploration and breakthrough in the mode of chondrocyte death — A potential new mechanism for osteoarthritis. Biomed Pharmacother. 2024;170:115990. doi: 10.1016/j.biopha.2023.115990 EDN: NZRAKY
  82. Farr JN, Xu M, Weivoda MM, et al. Targeting cellular senescence prevents age-related bone loss in mice. Nat Med. 2017;23(9):1072–1079. doi: 10.1038/nm.4385
  83. Chin AF, Han J, Clement CC, et al. Senolytic treatment reduces oxidative protein stress in an aging male murine model of post-traumatic osteoarthritis. Aging Cell. 2023;22(11):e13979. doi: 10.1111/acel.13979 EDN: ZQMXVC
  84. Liu Y, Zhang Z, Li T, et al. Senescence in osteoarthritis: from mechanism to potential treatment. Arthritis Res Ther. 2022;24(1):174. doi: 10.1186/s13075-022-02859-x EDN: AGQUGD
  85. Singh P, Kapahi P, van Deursen JM. Immune checkpoint inhibitors as senolytic agents. Cell Res. 2023;33(3):197–198. doi: 10.1038/s41422-022-00761-4 EDN: GPKHYQ
  86. Cao Z, Li Y, Wang W, et al. Is Lutikizumab, an anti-interleukin-1α/β dual variable domain immunoglobulin, efficacious for osteoarthritis? Results from a bayesian network meta-analysis. Biomed Res Int. 2020;2020:9013283. doi: 10.1155/2020/9013283 EDN: KGACZJ
  87. Schulze-Tanzil G. Experimental therapeutics for the treatment of osteoarthritis. J Exp Pharmacol. 2021;13:101–125. doi: 10.2147/JEP.S237479 EDN: PLJAEQ
  88. Xiong Y, Mi BB, Lin Z, et al. The role of the immune microenvironment in bone, cartilage, and soft tissue regeneration: from mechanism to therapeutic opportunity. Mil Med Res. 2022;9(1):65. doi: 10.1186/s40779-022-00426-8 EDN: YASGEE
  89. Reid P, Liew DF, Akruwala R, et al. Activated osteoarthritis following immune checkpoint inhibitor treatment: an observational study. J Immunother Cancer. 2021;9(9):e003260. doi: 10.1136/jitc-2021-003260 EDN: WHWFZL
  90. Hu Q, Ecker M. Overview of MMP-13 as a promising target for the treatment of osteoarthritis. Int J Mol Sci. 2021;22(4):1742. doi: 10.3390/ijms22041742 EDN: TJKTRH
  91. Rodriguez-Merchan EC. The current role of disease-modifying osteoarthritis drugs. Arch Bone Jt Surg. 2023;11(1):11–22. doi: 10.22038/ABJS.2021.56530.2807
  92. Li J, Zhang B, Liu WX, et al. Metformin limits osteoarthritis development and progression through activation of AMPK signalling. Ann Rheum Dis. 2020;79(5):635–645. doi: 10.1136/annrheumdis-2019-216713 EDN: NLRFMU
  93. Kong H, Sun ML, Zhang XA, Wang XQ. Crosstalk among circRNA/lncRNA, miRNA, and mRNA in osteoarthritis. Front Cell Dev Biol. 2021;9:774370. doi: 10.3389/fcell.2021.774370 EDN: EWKLPI
  94. Duan L, Liang Y, Xu X, et al. Recent progress on the role of miR-140 in cartilage matrix remodelling and its implications for osteoarthritis treatment. Arthritis Res Ther. 2020;22(1):194. doi: 10.1186/s13075-020-02290-0 EDN: LAIOMN
  95. He X, Deng L. miR-204-5p inhibits inflammation of synovial fibroblasts in osteoarthritis by suppressing FOXC1. J Orthop Sci. 2022;27(4):921–928. doi: 10.1016/j.jos.2021.03.014 EDN: NANQHP

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2026 Eco-Vector

License URL: https://eco-vector.com/for_authors.php#07

Согласие на обработку персональных данных

 

Используя сайт https://journals.rcsi.science, я (далее – «Пользователь» или «Субъект персональных данных») даю согласие на обработку персональных данных на этом сайте (текст Согласия) и на обработку персональных данных с помощью сервиса «Яндекс.Метрика» (текст Согласия).