Bone modeling in response to mechanical forces is mediated by biochemical and cellular events, many of which are still poorly understood. Although various cytokines have been implicated as mediators in this process, the role of TGF-betas have not been established; however, their documented effects on osteoblasts, osteoclasts and osteogenesis suggest a substantial role. We hypothesize that TGF-beta1 and TGF-beta2 mediate mechanically-induced bone modeling, and that sutural fibroblasts and periosteal osteoblasts synthesize these growth factors in direct response to external mechanical forces. To test these hypotheses, compressive of tensile forces, which result in periosteal bone resorption and bone formation, respectively, will be applied to (a) coronal sutures of young mice placed in culture media with or without antisense TGF-beta, and (b) to cultured sutural fibroblasts and calvarial osteoblasts. Tissue and cell-conditioned medium will be collected at prespecified times and assayed qualitatively and quantitatively for TGF-beta1 and TGF-beta2. The tissue explants will then be subjected to in situ hybridization for TGF-beta1 and TGF-beta2, and to histomorphometry for quantitating bone modeling. These experiments will provide the first insights into the role of TGF-betas in mechanically-induced bone modeling, and also aid in understanding the normal growth of craniofacial sutures, and the response of these sutures and the periodontal apparatus to orthodontic forces.
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