Yingchun Chen1, Lin Zhang1, Ernan Li1, Genai Zhang1, Yu Hou1, Wei Yuan1, Wei Qu1, Lixiang Ding2. 1. Department of Spinal Surgery, Beijing Shijitan Hospital, Beijing 100038, China. 2. Department of Spinal Surgery, Beijing Shijitan Hospital, Beijing 100038, China. Electronic address: dinglixiang@hotmail.com.
Abstract
AIMS: Cumulative evidence suggests that long-chain non-coding RNA (lncRNA) is involved in the pathogenesis of osteoarthritis (OA). The present study aimed to explore the regulatory role and related mechanisms of HOX transcript antisense intergenic RNA (HOTAIR) in OA. MATERIAL AND METHODS: The OA mouse model was constructed by the medial meniscus (DMM) method, and Interleukin (IL)-1β-induced chondrocytes were used to simulate OA in vitro. KEY FINDINGS: Results found that HOTAIR was significantly up-regulated in articular cartilage tissues of OA mice and IL-1β-induced chondrocytes, accompanied by down-regulation of miR-20b and increased expression of the phosphatase and tensin homolog (PTEN). HOTAIR silencing improved cartilage tissue damage in OA mice, and promoted the expression of collagen II and aggrecan in cartilage tissue, while inhibited the expression of matrix metalloproteinases (MMP)-13 and ADAMTS-5. Overexpression of HOTAIR inhibited the proliferation of IL-1β-induced chondrocytes and promoted apoptosis and extracellular matrix (ECM) degradation, whereas the effect of HOTAIR knockdown was reversed. Bioinformatics software and luciferase reporter experiments confirmed that HOTAIR could negatively regulate miR-20b, and PTEN was a target gene of miR-20b. An increase in PTEN expression induced by HOTAIR overexpression could be reversed by the introduction of miR-20b mimic. HOTAIR overexpression significantly reversed miR-20 mimic-mediated inhibition of apoptosis and ECM degradation in IL-1β-induced chondrocytes, whereas the introduction of si-HOTAIR eliminated anti-miR-20b-mediated apoptosis and ECM degradation. SIGNIFICANCE: HOTAIR can participate in OA by promoting chondrocyte apoptosis and ECM degradation, which may be related to its targeted regulation of miR-20b/PTEN axis.
AIMS: Cumulative evidence suggests that long-chain non-coding RNA (lncRNA) is involved in the pathogenesis of osteoarthritis (OA). The present study aimed to explore the regulatory role and related mechanisms of HOX transcript antisense intergenic RNA (HOTAIR) in OA. MATERIAL AND METHODS: The OA mouse model was constructed by the medial meniscus (DMM) method, and Interleukin (IL)-1β-induced chondrocytes were used to simulate OA in vitro. KEY FINDINGS: Results found that HOTAIR was significantly up-regulated in articular cartilage tissues of OA mice and IL-1β-induced chondrocytes, accompanied by down-regulation of miR-20b and increased expression of the phosphatase and tensin homolog (PTEN). HOTAIR silencing improved cartilage tissue damage in OA mice, and promoted the expression of collagen II and aggrecan in cartilage tissue, while inhibited the expression of matrix metalloproteinases (MMP)-13 and ADAMTS-5. Overexpression of HOTAIR inhibited the proliferation of IL-1β-induced chondrocytes and promoted apoptosis and extracellular matrix (ECM) degradation, whereas the effect of HOTAIR knockdown was reversed. Bioinformatics software and luciferase reporter experiments confirmed that HOTAIR could negatively regulate miR-20b, and PTEN was a target gene of miR-20b. An increase in PTEN expression induced by HOTAIR overexpression could be reversed by the introduction of miR-20b mimic. HOTAIR overexpression significantly reversed miR-20 mimic-mediated inhibition of apoptosis and ECM degradation in IL-1β-induced chondrocytes, whereas the introduction of si-HOTAIR eliminated anti-miR-20b-mediated apoptosis and ECM degradation. SIGNIFICANCE: HOTAIR can participate in OA by promoting chondrocyte apoptosis and ECM degradation, which may be related to its targeted regulation of miR-20b/PTEN axis.