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Maintaining hypoxia environment of subchondral bone alleviates osteoarthritis progression.
Zhang, Hao; Wang, Lipeng; Cui, Jin; Wang, Sicheng; Han, Yafei; Shao, Hongda; Wang, Cheng; Hu, Yan; Li, Xiaoqun; Zhou, Qirong; Guo, Jiawei; Zhuang, Xinchen; Sheng, Shihao; Zhang, Tao; Zhou, Dongyang; Chen, Jiao; Wang, Fuxiao; Gao, Qianmin; Jing, Yingying; Chen, Xiao; Su, Jiacan.
Afiliación
  • Zhang H; Department of Orthopedics, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, China.
  • Wang L; Institute of Translational Medicine, Shanghai University, Shanghai 200444, China.
  • Cui J; Department of Orthopedic, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
  • Wang S; Institute of Translational Medicine, Shanghai University, Shanghai 200444, China.
  • Han Y; Department of Orthopedics, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, China.
  • Shao H; Institute of Translational Medicine, Shanghai University, Shanghai 200444, China.
  • Wang C; Institute of Translational Medicine, Shanghai University, Shanghai 200444, China.
  • Hu Y; Department of Orthopedics, Shanghai Zhongye Hospital, Shanghai 200941, China.
  • Li X; Institute of Translational Medicine, Shanghai University, Shanghai 200444, China.
  • Zhou Q; Department of Nuclear Medicine, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.
  • Guo J; Department of Nuclear Medicine, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.
  • Zhuang X; Institute of Translational Medicine, Shanghai University, Shanghai 200444, China.
  • Sheng S; Department of Orthopedic, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
  • Zhang T; Department of Orthopedics, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, China.
  • Zhou D; Department of Orthopedics, No. 929 Hospital, Naval Medical University, Shanghai 200433, China.
  • Chen J; Department of Orthopedics, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, China.
  • Wang F; Department of Orthopedics, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, China.
  • Gao Q; Institute of Translational Medicine, Shanghai University, Shanghai 200444, China.
  • Jing Y; Department of Orthopedics, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, China.
  • Chen X; Department of Orthopedics, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, China.
  • Su J; Department of Orthopedics, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, China.
Sci Adv ; 9(14): eabo7868, 2023 04 05.
Article en En | MEDLINE | ID: mdl-37018403
Abnormal subchondral bone remodeling featured by overactivated osteoclastogenesis leads to articular cartilage degeneration and osteoarthritis (OA) progression, but the mechanism is unclear. We used lymphocyte cytosolic protein 1 (Lcp1) knockout mice to suppress subchondral osteoclasts in a mice OA model with anterior cruciate ligament transection (ACLT), and Lcp1-/- mice showed decreased bone remodeling in subchondral bone and retarded cartilage degeneration. For mechanisms, the activated osteoclasts in subchondral bone induced type-H vessels and elevated oxygen concentration, which ubiquitylated hypoxia-inducible factor 1 alpha subunit (HIF-1α) in chondrocytes and led to cartilage degeneration. Lcp1 knockout impeded angiogenesis, which maintained hypoxia environment in joints and delayed the OA progression. Stabilization of HIF-1α delayed cartilage degeneration, and knockdown of Hif1a abolished the protective effects of Lcp1 knockout. Last, we showed that Oroxylin A, an Lcp1-encoded protein l-plastin (LPL) inhibitor, could alleviate OA progression. In conclusion, maintaining hypoxic environment is an attractive strategy for OA treatment.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteoartritis / Cartílago Articular Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Sci Adv Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteoartritis / Cartílago Articular Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Sci Adv Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos