He Chunlei, Zhao Chang, Liu Sheng, Zhong Yanchun, Liu Lulin and Cai Daozhang* Pages 4613 - 4621 ( 9 )
Background: Osteoarthritis (OA) pertains to a chronic disease of degenerative joints distinguished by articular cartilage destruction, subchondral bone remodeling, osteophyte formation, and inflammatory changes. Chondrocyte apoptosis is inextricably linked to cartilage degeneration. SRY-related high-mobility-group-box 9 (SOX9) is a well-acknowledged transcription factor in the chondrogenesis. Nevertheless, the detailed function of miR-138-5p/SOX9 in OA remains to be fully clarified.
Materials and Methods: qRT-PCR was performed to measure the expressions of miR-138-5p and SOX9 mRNA in OA and normal cartilage tissues and cells. Human chondrocyte cell lines, CHON-001 and ATDC5, were treated with different doses of interleukin-1β (IL-1β) to simulate the inflammatory response environment of OA. miR-138-5p mimics, miR-138-5p inhibitors, and SOX9 small interfering RNA (siRNA) were constructed and transfected into CHON-001 and ATDC5 cells. CCK-8 was conducted to determine the cell viability and transwell assay was used to monitor the migration of cells. Western blot was carried out to detect the expressions of apoptosis- related factors. Enzyme-linked immunosorbent assay (ELISA) was adopted to measure the contents of inflammatory factors. TargetScan predicted SOX9 was a target gene of miR-138-5p, which was then verified by luciferase assay. Results: miR-138-5p expression was down-regulated in OA and regulated SOX9 expression. The downregulation of miR-138-5p facilitated the proliferation and migration of CHON-001 and ATDC5 cells, while impeded their apoptosis and inflammatory response. Besides, down-regulated SOX9 can counteract the promoting effect of down-regulated miR-138-5p on the proliferation and migration of chondrocytes. Conclusion: miR-138-5p can arrest the proliferation and migration of CHON-001 and ATDC5 via restraining SOX9, and facilitate the apoptosis and inflammation. This study revealed the protective effect of down-regulated miR-138-5p on the inflammatory injury of chondrocytes caused by IL-1β.miR-138-5p, SOX9, OA, proliferation, apoptosis, inflammation.
Department of Orthopedics, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, Guangdong, Department of Orthopedics, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, Guangdong, Department of Orthopedics, The First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, Jiangxi, Department of Orthopedics, The First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, Jiangxi, Department of Orthopedics, The First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, Jiangxi, Department of Orthopedics, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, Guangdong