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Roles and Mechanisms of Irisin in Attenuating Pathological Features of Osteoarthritis.
Li, Xiangfen; Zhu, Xiaofang; Wu, Hongle; Van Dyke, Thomas E; Xu, Xiaoyang; Morgan, Elise F; Fu, Wenyu; Liu, Chuanju; Tu, Qisheng; Huang, Dingming; Chen, Jake.
Afiliación
  • Li X; State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
  • Zhu X; Division of Oral Biology, Tufts University School of Dental Medicine, Boston, MA, United States.
  • Wu H; Division of Oral Biology, Tufts University School of Dental Medicine, Boston, MA, United States.
  • Van Dyke TE; State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
  • Xu X; Division of Oral Biology, Tufts University School of Dental Medicine, Boston, MA, United States.
  • Morgan EF; Clinical and Translational Research, Forsyth Institute, Cambridge, MA, United States.
  • Fu W; Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA, United States.
  • Liu C; Department of Chemical and Materials Engineering, New Jersey Institute of Technology, Newark, NJ, United States.
  • Tu Q; Department of Mechanical Engineering, Boston University, Boston, MA, United States.
  • Huang D; Department of Orthopedics Surgery, New York University School of Medicine, New York, NY, United States.
  • Chen J; Department of Cell Biology, New York University School of Medicine, New York, NY, United States.
Front Cell Dev Biol ; 9: 703670, 2021.
Article en En | MEDLINE | ID: mdl-34650969
To investigate the effects and mechanisms of irisin, a newly discovered myokine, in cartilage development, osteoarthritis (OA) pathophysiology and its therapeutic potential for treating OA we applied the following five strategical analyses using (1) murine joint tissues at different developmental stages; (2) human normal and OA pathological tissue samples; (3) experimental OA mouse model; (4) irisin gene knockout (KO) and knock in (KI) mouse lines and their cartilage cells; (5) in vitro mechanistic experiments. We found that Irisin was involved in all stages of cartilage development. Both human and mouse OA tissues showed a decreased expression of irisin. Intra-articular injection of irisin attenuated ACLT-induced OA progression. Irisin knockout mice developed severe OA while irisin overexpression in both irisin KI mice and intraarticular injection of irisin protein attenuated OA progression. Irisin inhibited inflammation and promoted anabolism in chondrogenic ADTC5 cells. Proliferative potential of primary chondrocytes from KI mice was found to be enhanced, while KO mice showed an inhibition under normal or inflammatory conditions. The primary chondrocytes from irisin KI mice showed reduced expression of inflammatory factors and the chondrocytes isolated from KO mice showed an opposite pattern. In conclusion, it is the first time to show that irisin is involved in cartilage development and OA pathogenesis. Irisin has the potential to ameliorate OA progression by decreasing cartilage degradation and inhibiting inflammation, which could lead to the development of a novel therapeutic target for treating bone and cartilage disorders including osteoarthritis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Front Cell Dev Biol Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Front Cell Dev Biol Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Suiza