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

Abstract

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.Cite this article: R-K. Zhang, G-W. Li, C. Zeng, C-X. Lin, L-S. Huang, G-X. Huang, C. Zhao, S-Y. Feng, H. Fang. Mechanical stress contributes to osteoarthritis development through the activation of transforming growth factor beta 1 (TGF-β1). Bone Joint Res 2018;7:587–594. DOI: 10.1302/2046-3758.711.BJR-2018-0057.R1.

Less mechanical loading attenuates osteoarthritis by reducing cartilage degeneration, subchondral bone remodelling, secondary inflammation, and activation of NLRP3 inflammasome

“…The pathogenesis of OA is multifactorial with many contributing factors, and repetitive and excessive joint loading is a well-accepted risk factor for OA. 23 – 25 It was reported that weight loading can result in abnormal mechanical stress in joints and increase the risk of OA, while less mechanical loading was thought to be beneficial for disease progression. 23 – 25 However, robust and detailed evidence is absent.…”

“… 23 – 25 It was reported that weight loading can result in abnormal mechanical stress in joints and increase the risk of OA, while less mechanical loading was thought to be beneficial for disease progression. 23 – 25 However, robust and detailed evidence is absent. Our study is the first to reveal that less mechanical loading can alleviate both cartilage damage and subchondral bone remodelling, and also inflammation in OA rats.…”

Bioinformatics analysis reveals different gene expression patterns in chondrocytes from knee and finger joints: implications for the effect of mechanical stress in the osteoarthritic development

“…Actually, these predicted miRNAs and pathways played important roles in OA has been verified in previous studies. Zhang et al have suggested that mechanical stress contributes to osteoarthritis development through the activation of TGF-β signaling pathway [5]. In addition, some professores suggested that circulating miRNAs, for example, miR-19b-3p and miR-122-5p, are promising biomarkers to diagnose knee OA [48,49].…”

“…Physiological dynamic loading exerts chondroprotective effect via initiating anti-catabolic and anti-inflammatory signals involved in chondrocyte homeostasis [3,4]. Pathologically, mechanical stimulation contributes to the activation of catabolic processes by altering specific signal pathway [5,6] and even involves in the induction of chondrocyte apoptosis [7]. Typically, when the chondrocyte homeostasis is disturbed by mechanical loading, articular cartilage destruction and degeneration occur, resulting in joint pain and dysfunction, clinically identified as osteoarthritis (OA) [8].…”

Knockout of miR-21-5p alleviates cartilage matrix degradation by targeting Gdf5 in temporomandibular joint osteoarthritis

“… 1 , 2 The condylar cartilage, joint disc, and glenoid fossa are key components of the TMJ, but these structural surfaces are not completely matched with each other. Thus, stress concentrations are generated in the contact area if these surfaces are in inappropriate contact, 3 which would causes serious damage and injury to the TMJ. Then, these surfaces erode and increasingly roughen, leading to pain and dysfunction.…”