MicroRNA-34a-5p promotes the progression of osteoarthritis secondary to developmental dysplasia of the hip by restraining SESN2-induced autophagy

Wang, Jun1,2,3; Li, Xiaopeng1; Guo, Xiang4; Wang, Congcong1; Liu, Zezhong1; Liu, Xiaoguang1; Sun, Yanshan1; Chen, Xiaohua5,7; Zhang, Yimin1,8; Chen, Gaoyang6,9

2023-06-01

10.1002/jor.25639

JOURNAL OF ORTHOPAEDIC RESEARCH   Impact Factor & Quartile

0736-0266

1554-527X

Osteoarthritis (OA), a late-stage complication of developmental dysplasia of the hip (DDH), is a key factor leading to further degeneration of joint function. Studies have shown that Sestrin2 (SESN2) is a positive regulator in protecting articular cartilage from degradation. However, the regulatory effects of SESN2 on DDH-OA and its upstream regulators remain obscure. Here, we first identified that the expression of SESN2 significantly decreased in the cartilage of DDH-OA samples, with an expression trend negatively correlated with OA severity. Using RNA sequencing, we identified that the upregulation of miR-34a-5p may be an important factor for the decrease in SESN2 expression. Further exploring the regulation mechanism of miR-34a-5p/SESN2 is of great significance for understanding the mechanism of DDH occurrence and development. Mechanistically, we showed that miR-34a-5p could significantly inhibit the expression of SESN2, thereby promoting the activity of the mTOR signaling pathway. We also found that miR-34a-5p significantly inhibited SESN2-induced autophagy, thereby suppressing the proliferation and migration of chondrocytes. We further validated that knocking down miR-34a-5p in vivo resulted in a significant increase in SESN2 expression and autophagy activity in DDH-OA cartilage. Our study suggests that miR-34a-5p is a negative regulator of DDH-OA, and may provide a new target for the prevention of DDH-OA.

autophagy developmental dysplasia of the hip miR-34a-5p osteoarthritis Sestrin2

SCI

English

Corresponding

Natural Science Foundation of Shandong Province["ZR2019PH026","ZR2020MH094"] ; Medical and Health Science and Technology Development Project of Shandong Province[202004070241] ; Shenzhen Municipal Science and Technology Innovation Committee Project["JCYJ20220530152812028","JCYJ2020010914422815"] ; Sanming Project of Medicine in Shenzhen[SZSM202111015] ; Shenzhen Key Laboratory of Musculoskeletal Tissue Reconstruction and Function Restoration[ZDSYS20200811143752005]

Orthopedics

Orthopedics

WOS:001012988900001

WILEY

CLINICAL MEDICINE

Web of Science

1.Weifang Med Univ, Affiliated Hosp 1, Weifang Peoples Hosp, Dept Orthoped, Weifang, Peoples R China
2.Capital Med Univ, Sch Rehabil Med, Beijing, Peoples R China
3.Beijing Boai Hosp, China Rehabil Res Ctr, Dept Neurol Rehabil, Beijing, Peoples R China
4.Weifang Med Univ, Affiliated Hosp, Dept Orthoped, Weifang, Peoples R China
5.Weifang Med Univ, Affiliated Hosp 1, Weifang Peoples Hosp, Dept Nucl Med, Weifang, Peoples R China
6.Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Affiliated Hosp 1, Dept Hand Surg,Shenzhen Key Lab Musculoskeletal Ti, Shenzhen, Peoples R China
7.Weifang Med Univ, Affiliated Hosp 1, Dept Nucl Med, Weifang 261000, Peoples R China
8.Weifang Med Univ, Affiliated Hosp 1, Dept Bone & Joint Surg, Weifang 261000, Peoples R China
9.Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen Peoples Hosp, Dept Hand Surg,Shenzhen Key Lab Musculoskeletal Ti, Shenzhen 518020, Peoples R China

Wang, Jun,Li, Xiaopeng,Guo, Xiang,et al. MicroRNA-34a-5p promotes the progression of osteoarthritis secondary to developmental dysplasia of the hip by restraining SESN2-induced autophagy[J]. JOURNAL OF ORTHOPAEDIC RESEARCH,2023.

Wang, Jun.,Li, Xiaopeng.,Guo, Xiang.,Wang, Congcong.,Liu, Zezhong.,...&Chen, Gaoyang.(2023).MicroRNA-34a-5p promotes the progression of osteoarthritis secondary to developmental dysplasia of the hip by restraining SESN2-induced autophagy.JOURNAL OF ORTHOPAEDIC RESEARCH.

Wang, Jun,et al."MicroRNA-34a-5p promotes the progression of osteoarthritis secondary to developmental dysplasia of the hip by restraining SESN2-induced autophagy".JOURNAL OF ORTHOPAEDIC RESEARCH (2023).