A study for role of small GTPases in mechanical stress response of chondocytes

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Cartilage is one of the major skeletal elements responding to mechanical stimulations that support not only temporomandibular joint function but also joints in the body, trachea, ear and nasal septurn. All these cartilages play major roles in the growth of skeletons as well as resisting to mechanical loading in the body. It is extremely important to clarify the mechanisms how chondrocytes differentiate and how chondrocytes produce their specific macromolecules and degrade them to clarify the mechanisms of facial growth and development of joint diseases. Especially, verifying the mechanisms and factors that regulates chondrocyte proliferation, differentiation and metabolismis critical for the development of the field of orthodontics. In our previous studies, we discovered that the sharing stress and/or tensile stress inhibited differentiation of chondrocytes derived from embryonic stem cells and maturation of chondrocytes in secondary cartilages such as mandibular condylar cartilages an … More d midpalatal suture cartilages. At the same time, tensile stress induced de-differentiation of chondrocytes as well. Contrary, compressive force enhanced the differentiation of chondrocytes. These revealed that the quantitative and qualitative difference of mechanical stress loaded on chondrocytes induces different responses of chondrogenic mesenchymal cells.In the present study, we verified the role of itnracellular tyrosine kinase pathway in mechanical stress response of chondrocytes focusing on the phospholyration of extracellular signal-regulated kinase (ERK)-1/2 and activation of small GTPase, Rho. Mesenchymal cells derived from embryonic rat limb bud was used for the present study. By using micromass culture system and mechanical stress loading system utilizing Flexcer Cell plate, activation and gene expression of ERK-1/2 and Rho was quatitated. Immediately after force loading (in 30 min), Rho was activated and peaked at 60min with up-regulation of gene expression. At the same time, ERK-1/2 was phospholyrated in 60 min after force loading while gene expression was not stimulated This mechanical stimulation resulted in the inhibition of chondrogenesis. Thus, these molecules play pivotal roles in the mechanical stress of differentiating chondrocytes. Less