Down-regulation of MiR-138-5p Protects Chondrocytes ATDC5 and CHON-001 from IL-1 β-induced Inflammation Via Up-regulating SOX9

Author(s): He Chunlei, Zhao Chang, Liu Sheng, Zhong Yanchun, Liu Lulin, Cai Daozhang*.

Journal Name: Current Pharmaceutical Design

Volume 25 , Issue 43 , 2019

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Abstract:

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.

Keywords: miR-138-5p, SOX9, OA, proliferation, apoptosis, inflammation.

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VOLUME: 25
ISSUE: 43
Year: 2019
Page: [4613 - 4621]
Pages: 9
DOI: 10.2174/1381612825666190905163046
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