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Unveiling the Role of Sik1 in Osteoblast Differentiation: Implications for Osteoarthritis.
Tian, Kuanmin; He, Xiaoxin; Lin, Xue; Chen, Xiaolei; Su, Yajing; Lu, Zhidong; Chen, Zhirong; Zhang, Liang; Li, Peng; Ma, Long; Lan, Zhibin; Zhao, Xin; Fen, Gangning; Hai, Qinqin; Xue, Di; Jin, Qunhua.
Afiliação
  • Tian K; The Third Ward of Orthopaedic Department, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, China.
  • He X; The Third Ward of Orthopaedic Department, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, China.
  • Lin X; Institute of Osteoarthropathy, Ningxia Key Laboratory of Clinical and Pathogenic Microbiology, Institute of Medical Sciences, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, China.
  • Chen X; The Third Ward of Orthopaedic Department, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, China.
  • Su Y; Institute of Osteoarthropathy, Ningxia Key Laboratory of Clinical and Pathogenic Microbiology, Institute of Medical Sciences, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, China.
  • Lu Z; First Clinical Medical School, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, P.R. China.
  • Chen Z; First Clinical Medical School, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, P.R. China.
  • Zhang L; First Clinical Medical School, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, P.R. China.
  • Li P; First Clinical Medical School, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, P.R. China.
  • Ma L; First Clinical Medical School, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, P.R. China.
  • Lan Z; The Third Ward of Orthopaedic Department, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, China.
  • Zhao X; First Clinical Medical School, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, P.R. China.
  • Fen G; Institute of Osteoarthropathy, Ningxia Key Laboratory of Clinical and Pathogenic Microbiology, Institute of Medical Sciences, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, China.
  • Hai Q; The Third Ward of Orthopaedic Department, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, China.
  • Xue D; Institute of Osteoarthropathy, Ningxia Key Laboratory of Clinical and Pathogenic Microbiology, Institute of Medical Sciences, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, China.
  • Jin Q; Institute of Osteoarthropathy, Ningxia Key Laboratory of Clinical and Pathogenic Microbiology, Institute of Medical Sciences, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, China.
Mol Cell Biol ; : 1-18, 2024 Aug 22.
Article em En | MEDLINE | ID: mdl-39169784
ABSTRACT
Osteoarthritis (OA) is a chronic degenerative disease characterized by subchondral osteosclerosis, mainly due to osteoblast activity. This research investigates the function of Sik1, a member of the AMP-activated protein kinase family, in OA. Proteomic analysis was conducted on clinical samples from 30 OA patients, revealing a negative correlation between Sik1 expression and OA. In vitro experiments utilized BMSCs to examine the effect of Sik1 on osteogenic differentiation. BMSCs were cultured and induced toward osteogenesis with specific media. Sik1 overexpression was achieved through lentiviral transfection, followed by analysis of osteogenesis-associated proteins using Western blotting, RT-qPCR, and alkaline phosphate staining. In vivo experiments involved destabilizing the medial meniscus in mice to establish an OA model, assessing the therapeutic potential of Sik1. The CT scans and histological staining were used to analyze subchondral bone alterations and cartilage damage. The findings show that Sik1 downregulation correlates with advanced OA and heightened osteogenic differentiation in BMSCs. Sik1 overexpression inhibits osteogenesis-related markers in vitro and reduces cartilage damage and subchondral osteosclerosis in vivo. Mechanistically, Sik1 modulates osteogenesis and subchondral bone changes through Runx2 activity regulation. The research emphasizes Sik1 as a promising target for treating OA, suggesting its involvement in controlling bone formation and changes in the subchondral osteosclerosis.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Mol Cell Biol Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Mol Cell Biol Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China País de publicação: Estados Unidos