Compressive Mechanical Stress Mediated Pathological Changes Of Mandibular Condylar Cartilage Is Regulated By Wnt Signaling Pathway

Part1:The effect of Wnt signaling pathway on rat mandibular condylar chondrocytes proliferated ratesObjective:To examine underlying mechanisms for the proliferation inhibition and its roles in mandibular cartilage thinning, we investigated the roles of Wnt signaling, which is important to physiological chondrocytes proliferation, in condylar chondrocyte proliferation inhibition and mandibular cartilage thinning during mechanical stress loading.Methods:Mechanical force-mediated cartilage thinning was induced by an established animal model to examine Wnt signaling activation. Histological changes in condylar cartilage were assessed by Hematoxylin & Eosin (HE). Immunohistochemistry and real-time PCR were performed to evaluate the Writ signaling activation and chondrocyte proliferation. Force-induced Wnt signaling was restored by a GSK3β inhibitor in vivo to evaluate its effects on chondrocyte and condylar cartilage.Results:Wnt signaling was largely compromised at late phase of mechanical force loading-mediated thinning. Specifically, Restoration of Wnt singling by GSK-3β inhibition at late stage, instead of early stage, significantly promoted the proliferation of condylar chondrocytes. Mechanistically, the reduced Cyclin D and Phospho-Histone H3 (H3) were largely recovered by GSK-3β inhibition in mechanical stress-treated chondrocytes.Conclusion:Wnt signaling is inhibited by mechanical stress, which leads to impaired proliferation in chondrocytes and consequently, cartilage thinning. Its restoration largely recovered the proliferation and cartilage thinning induced by mechanical stress.Part2:Research on the Wnt signaling pathway on pathological changes in rat mandibular condylar cartilage under compressive mechanical stressObjective:To investigate the roles of Wnt signaling pathway on pathological changes in rat mandibular condylar cartilage under compressive mechanical stress. We investigated the roles of Wnt signaling, which is already proved to be important to proliferatd physiological chondrocytes, in maintaining ECM homeostasis and inflammatory responses.Methods:Histological changes in condylar cartilage were assessed by Alcian blue (Ab). Immunohistochemistry of Col-Ⅱ and TNF-α, real-time PCR of Col-Ⅱ, Col-X, MMPs, TNF-αand IL-1were performed to evaluate the protease activation and chondrocyte ECM homeostasis.Results:Restoration of Wnt singling by GSK-3β inhibition at late stage significantly inhibited the activation of MMPs which upregulated the expression of collagen and Proteoglycan. Furthermore, the increased TNF-αand IL-1 were largely down-regulated by GSK-3β inhibition in mechanical stress-treated chondrocytes.Conclusion:Wnt signaling is inhibited by mechanical stress, which leads to impaired ECM in chondrocytes and activated inflammatory progress. Its restoration largely stabilise the ECM homeostasis and inflammatory progress induced by mechanical stress.