Regulation of commicroRNA-22 on chondrocyte senescence by inhibiting SIRT1 expression
YAN Shiju1, DONG Wenjing2, LI Zhirui1, ZHAO Yanpeng3, HAN Tao1, WEI Junqiang1, WANG Junliang1, LIN Feng1
1. Department of Orthopedics; 2. Department of Gerontology, Hainan Hospital of Chinese PLA General Hospital, Sanya 572013, China; 3. Department of Orthopedics, the Fourth Medical Center of Chinese PLA General Hospital, Beijing 100048, China
Abstract：Objective To investigate the effects of microRNA-22 on chondrocyte senescence in osteoarthritis. Methods Primary chondrocytes were collected from OA cartilage and divided into miR-22 mimics group, miR-22 inhibitor group and Negative Control (NC) group, which were transfected with miR-22 mimics, miR-22 inhibitor and negative control respectively. MTT assay was used to detect the effects of microRNA-22 on cell proliferation of chondrocyte; senescence-associated β-galactosidase (SA-β-Gal) staining was performed to evaluate the effects of microRNA-22 on senescence of chondrocyte. Western blot was used to detect the expression level of SIRT1 and P16. Results Compared with Negative Control (NC) group, the proliferation rate of chondrocytes was significantly inhibited in miR-22 mimics group and upregulated in miR-22 inhibitor group. The ratio of SA-β-Gal-positive chondrocytes group was elevated in miR-22 mimics and downregulated in miR-22 inhibitor group. After chondrocytes were transfected with miR-22 mimics, the expression level of P16 was promoted while SIRT1 was inhibited. On the contrary, the expression level of P16 was decreased while SIRT1 was elevated after chondrocytes were transfected with miR-22 inhibitor. Conclusions For OA, microRNA-22 could inhibit chondrocyte proliferation, as well as promote chondrocyte senescence by regulating SIRT1 and P16, so microRNA-22 could be a novel target of OA treatment.
Hunter D J, Bierma-Zeinstra S. Osteoarthritis[J]. Lancet, 2019,393(10182):1745-1759.
[3]
Abramoff B, Caldera F E. Osteoarthritis: pathology, diagnosis, and treatment options[J]. Med Clin North Am, 2020,104(2):293-311.
[4]
Hayflick L, Moorhead P S. The serial cultivation of human diploid cell strains[J]. Exp Cell Res, 1961,25:585-621.
[5]
Sharpless N E, Sherr C J. Forging a signature of in vivo senescence[J]. Nat Rev Cancer, 2015, 15(7):397-408.
[6]
Campisi J, Kapahi P, Lithgow G J, et al. From discoveries in ageing research to therapeutics for healthy ageing[J]. Nature, 2019,571(7764):183-192.
[7]
Vina E R, Kwoh C K. Epidemiology of osteoarthritis: literature update[J]. Curr Opin Rheumatol, 2018,30(2):160-167.
[8]
Zhao L, Hu K, Cao J, et al. lncRNA miat functions as a ceRNA to upregulate sirt1 by sponging miR-22-3p in HCC cellular senescence[J]. Aging (Albany NY), 2019,11(17):7098-7122.
[9]
Li P, Mao W W, Zhang S, et al. Sodium hydrosulfide alleviates dexamethasone-induced cell senescence and dysfunction through targeting the miR-22/sirt1 pathway in osteoblastic MC3T3-E1 cells[J]. Exp Ther Med, 2021,21(3):238.
Hawker G A, King L K. The burden of osteoarthritis in older adults[J]. Clin Geriatr Med, 2022,38(2):181-192.
[12]
Abdel-Aziz M A, Ahmed H, El-Nekeety A A, et al. Osteoarthritis complications and the recent therapeutic approaches[J]. Inflammopharmacology, 2021,29(6):1653-1667.
[13]
Favero M, Belluzzi E, Ortolan A, et al. Erosive hand osteoarthritis: latest findings and outlook[J]. Nat Rev Rheumatol, 2022,18(3):171-183.
[14]
Goldring M B. The role of the chondrocyte in osteoarthritis[J]. Arthritis Rheum, 2000, 43(9): 1916-1926.
[15]
Coryell P R, Diekman B O, Loeser R F. Mechanisms and therapeutic implications of cellular senescence in osteoarthritis[J]. Nat Rev Rheumatol, 2021,17(1):47-57.
[16]
Zhang H, Shao Y, Yao Z, et al. Mechanical overloading promotes chondrocyte senescence and osteoarthritis development through downregulating FBXW7[J]. Ann Rheum Dis, 2022, 81(5): 676-686.
[17]
Lu H, Jia C, Wu D, et al. Fibroblast growth factor 21 (FGF21) alleviates senescence, apoptosis, and extracellular matrix degradation in osteoarthritis via the SIRT1-mTOR signaling pathway[J]. Cell Death Dis, 2021,12(10):865.
[18]
Chen H, Qin J, Shi H, et al. Rhoifolin ameliorates osteoarthritis via the Nrf2/NF-kappaB axis: in vitro and in vivo experiments[J]. Osteoarthritis Cartilage, 2022,30(5):735-745.
[19]
Xu C, Liu C H, Zhang D L. MicroRNA-22 inhibition prevents doxorubicin-induced cardiotoxicity via upregulating SIRT1[J]. Biochem Biophys Res Commun, 2020, 521(2): 485- 491.
[20]
Pardo P S, Boriek A M. SIRT1 regulation in ageing and obesity[J]. Mech Ageing Dev, 2020, 188:111249.
[21]
Chen C, Zhou M, Ge Y, et al. SIRT1 and aging related signaling pathways[J]. Mech Ageing Dev, 2020,187:111215.
[22]
Deng Z, Li Y, Liu H, et al. The role of sirtuin 1 and its activator, resveratrol in osteoarthritis[J]. Biosci Rep, 2019,39(5).
[23]
Xiong G, Yang Y, Guo M. Effect of resveratrol on abnormal bone remodeling and angiogenesis of subchondral bone in osteoarthritis[J]. Int J Clin Exp Pathol, 2021,14(4):417-425.
[24]
Guo G E, Ma L W, Jiang B, et al. Hydrogen peroxide induces p16(INK4a) through an AUF1-dependent manner[J]. J Cell Biochem, 2010,109(5):1000-1005.
[25]
Hernandez-Segura A, Nehme J, Demaria M. Hallmarks of cellular senescence[J]. Trends Cell Biol, 2018,28(6):436-453.
[26]
Loeser R F. Aging and osteoarthritis: the role of chondrocyte senescence and aging changes in the cartilage matrix[J]. Osteoarthritis Cartilage, 2009,17(8):971-979.
[27]
Diekman B O, Sessions G A, Collins J A, et al. Expression of p16(INK) (4a) is a biomarker of chondrocyte aging but does not cause osteoarthritis[J]. Aging Cell, 2018,17(4):e12771.
2023, Vol. 34 
