Chronic inflammation in the oral cavity is usually provoked by interactions between the bacterial inhabitants of the mouth and the host. The accumulation of chronic inflammatory cells in the gingiva leads to the production of a family of locally active osteotropic factors (formerly called osteoclast activating factor of OAF), which are presumably responsible for the destruction of alveolar bone which occurs in periodontal disease. Transforming growth factor beta (TGF beta) is an immune cell product which is also abundant in bone and is released when bone is resorbed. The role of TGF beta and the cartilage-inducing factor Beta (CIFB) related protein in modulation of bone cell activity is still unclear. In this proposal, we plan to examine the interactions between TGF beta and other cytokines on both bone resorption and parameters of bone formation in vitro. Since TGF beta is released by bone in a latent form and is activated by acid exposure, and acid production is an essential component of the bone resorption process, we will examine the role of CIFB, a molecule homologous to TGF beta, in the bone remodeling process and in relation to other cytokines. Bone resorption will be assessed by measuring 45Ca release from previously labeled fetal rat long bones and neonatal mouse calvaria. The effect of cytokines on osteoclast formation will be evaluated using the modified Dexter marrow culture system in which osteoclast-like cells form in vitro. These experiments should clarify the mechanism of osteoclastic bone destruction in periodontal disease as well as other chronic inflammatory diseases, and may lead to insight as to how this bone destruction can be prevented or alleviated.
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