Mechanical stress contributes to osteoarthritis development through the activation of transforming growth factor beta 1 (TGF-β1)

Bone & Joint Research

article

R-K. Zhang¹  G-W. Li²  C. Zeng¹  C-X. Lin¹  L-S. Huang³  G-X. Huang¹  C. Zhao¹  S-Y. Feng⁴  H. Fang¹ 

[1] Department of Orthopedics, Academy of Orthopedics Guangdong Province, Orthopedic Hospital of Guangdong Province, The Third Affiliated Hospital of Southern Medical University;Department of Orthopaedics of The Fifth Affiliated Hospital of Sun Yat-sen University;Department of Clinical Laboratory, Sun Yat-sen Memorial Hospital of Sun Yat-sen University;Department of Otolaryngology of The Fifth Affiliated Hospital of Sun Yat-sen University

关键词: Osteoarthritis;    TGF-β1;    Mechanical stress;   

DOI  :  10.1302/2046-3758.711.BJR-2018-0057.R1

学科分类：骨科学

来源: British Editorial Society Of Bone And Joint Surgery

【 摘 要 】

ObjectivesThe role of mechanical stress and transforming growth factor beta 1 (TGF-β1) is important in the initiation and progression of osteoarthritis (OA). However, the underlying molecular mechanisms are not clearly known.MethodsIn this study, TGF-β1 from osteoclasts and knee joints were analyzed using a co-cultured cell model and an OA rat model, respectively. Five patients with a femoral neck fracture (four female and one male, mean 73.4 years (68 to 79)) were recruited between January 2015 and December 2015. Results showed that TGF-β1 was significantly upregulated in osteoclasts by cyclic loading in a time- and dose-dependent mode. The osteoclasts were subjected to cyclic loading before being co-cultured with chondrocytes for 24 hours.ResultsA significant decrease in the survival rate of co-cultured chondrocytes was found. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling (TUNEL) assay demonstrated that mechanical stress-induced apoptosis occurred significantly in co-cultured chondrocytes but administration of the TGF-β1 receptor inhibitor, SB-505124, can significantly reverse these effects. Abdominal administration of SB-505124 can attenuate markedly articular cartilage degradation in OA rats.ConclusionMechanical stress-induced overexpression of TGF-β1 from osteoclasts is responsible for chondrocyte apoptosis and cartilage degeneration in OA. Administration of a TGF-β1 inhibitor can inhibit articular cartilage degradation.

【 授权许可】

CC BY-NC