RUNX2 stabilization by long non-coding RNAs contributes to hypertrophic changes in human chondrocytes

作者：Dong Suk Yoon, Eun‐Ji Kim, Sehee Cho, Soyeong Jung, Kyoungmi Lee, Kwang Hwan Park, Jin Woo Lee, Sung‐Hwan Kim · 发表于：International Journal of Biological Sciences · 年份：2022 · DOI：10.7150/ijbs.74895 · 被引用次数：27 · 研究领域：Cancer-related molecular mechanisms research、Osteoarthritis Treatment and Mechanisms、RNA Research and Splicing

Background: Chondrocyte hypertrophy has been implicated in endochondral ossification and osteoarthritis (OA). In OA, hypertrophic chondrocytes contribute to the destruction and focal calcification of the joint cartilage. Although studies in this field have remarkably developed the modulation of joint inflammation using gene therapy and regeneration of damaged articular cartilage using cell therapy, studies that can modulate or prevent hypertrophic changes in articular chondrocytes are still lacking. Methods: In vitro hypertrophic differentiation and inflammation assays were conducted using human normal chondrocyte cell lines, TC28a2 cells. Human cartilage tissues and primary articular chondrocytes were obtained from OA patients undergoing total knee arthroplasty. Long non-coding RNAs (lncRNAs), LINC02035 and LOC100130207, were selected through RNA-sequencing analysis using RNAs extracted from TC28a2 cells cultured in hypertrophic medium. The regulatory mechanism was evaluated using western blotting, real-time quantitative polymerase chain reaction, osteocalcin reporter assay, RNA-immunoprecipitation (RNA-IP), RNA-in situ hybridization, and IP. Results: LncRNAs are crucial regulators of various biological processes. In this study, we identified two important lncRNAs, LINC02035 and LOC100130207, which play important roles in hypertrophic changes in normal chondrocytes, through RNA sequencing. Interestingly, the expression level of RUNX2, a master regulator of chondrocyte hypert...