Yu Xiao1, Xu Yan2, Yang Yang2, Xinlong Ma2. 1. Department of Joint Surgery, Tianjin Hospital, Hexi, Tianjin, 300211, China. Electronic address: yuxiao2237@126.com. 2. Department of Orthopaedic Surgery, Tianjin Hospital, Hexi, Tianjin, 300211, China.
Abstract
OBJECTIVE: Osteoarthritis (OA) is a leading cause of pain and disability worldwide, which is characterized by degenerative and inflammatory processes affecting joints and surrounding tissues. This study aimed to elucidate the role and possible mechanism of long non-coding RNA HOX antisense intergenic RNA myeloid 1 variant 1 (HOTAIRM1-1) in the development of osteoarthritis (OA). MATERIAL AND METHODS: The expressions of HOTAIRM1-1 and miR-125b in OA cartilages and normal articular cartilages were determined. Moreover, human mesenchymal stem cells (MSCs) were cultured in MSC growth medium for 8 days to induce chondrogenic differentiation. The effects of aberrant expression of HOTAIRM1-1 on MSCs viability, apoptosis and differentiation were investigated. Furthermore, the regulatory relationships between HOTAIRM1-1 and miR-125b as well as the target of miR-125b were explored. Besides, the association between HOTAIRM1-1 and JNK/MAPK/ERK pathway was detected. RESULTS: Inverse expression of HOTAIRM1-1 (downregulated) and miR-125b (upregulated) was revealed in OA cartilages. In addition, HOTAIRM1-1 expression increased at 4 days after induction of chondrogenic differentiation and further enhanced after 8 days, while miR-125b had opposite expression changes. Suppression of HOTAIRM1-1 inhibited MSCs viability, induced apoptosis and suppressed cell differentiation. Moreover, HOTAIRM1-1 negatively regulated the expression of miR-125b, and the effects of HOTAIRM1-1 suppression on cell viability, apoptosis and differentiation were achieved by negative regulation of miR-125b. Furthermore, miR-125b regulated MSCs viability, apoptosis and differentiation via targeting bone morphogenetic protein receptor 2 (BMPR2). Besides, overexpression of HOTAIRM1-1 inhibited the activation of JNK/MAPK/ERK pathway. CONCLUSIONS: Our results indicate that HOTAIRM1-1 is downregulated in OA cartilages, and its downregulation may inhibit MSCs viability, induce apoptosis and suppress differentiation via regulating miR-125b/BMPR2 axis. JNK/MAPK/ERK pathway may be a possible downstream mechanism to mediate the role of HOTAIRM1-1 in OA development.
OBJECTIVE:Osteoarthritis (OA) is a leading cause of pain and disability worldwide, which is characterized by degenerative and inflammatory processes affecting joints and surrounding tissues. This study aimed to elucidate the role and possible mechanism of long non-coding RNA HOX antisense intergenic RNA myeloid 1 variant 1 (HOTAIRM1-1) in the development of osteoarthritis (OA). MATERIAL AND METHODS: The expressions of HOTAIRM1-1 and miR-125b in OA cartilages and normal articular cartilages were determined. Moreover, human mesenchymal stem cells (MSCs) were cultured in MSC growth medium for 8 days to induce chondrogenic differentiation. The effects of aberrant expression of HOTAIRM1-1 on MSCs viability, apoptosis and differentiation were investigated. Furthermore, the regulatory relationships between HOTAIRM1-1 and miR-125b as well as the target of miR-125b were explored. Besides, the association between HOTAIRM1-1 and JNK/MAPK/ERK pathway was detected. RESULTS: Inverse expression of HOTAIRM1-1 (downregulated) and miR-125b (upregulated) was revealed in OA cartilages. In addition, HOTAIRM1-1 expression increased at 4 days after induction of chondrogenic differentiation and further enhanced after 8 days, while miR-125b had opposite expression changes. Suppression of HOTAIRM1-1 inhibited MSCs viability, induced apoptosis and suppressed cell differentiation. Moreover, HOTAIRM1-1 negatively regulated the expression of miR-125b, and the effects of HOTAIRM1-1 suppression on cell viability, apoptosis and differentiation were achieved by negative regulation of miR-125b. Furthermore, miR-125b regulated MSCs viability, apoptosis and differentiation via targeting bone morphogenetic protein receptor 2 (BMPR2). Besides, overexpression of HOTAIRM1-1 inhibited the activation of JNK/MAPK/ERK pathway. CONCLUSIONS: Our results indicate that HOTAIRM1-1 is downregulated in OA cartilages, and its downregulation may inhibit MSCs viability, induce apoptosis and suppress differentiation via regulating miR-125b/BMPR2 axis. JNK/MAPK/ERK pathway may be a possible downstream mechanism to mediate the role of HOTAIRM1-1 in OA development.