歯周組織の破壊と再生におけるサイトカインの役割について

Abstract

Inflammatory bone resorption is a feature of chronic inflammatory diseases such as periodontitis and rheumatoid arthritis. In human periodontitis, certain species of Gramnegative bacteria harbored in periodontal pockets play a major part in the pathogenesis of the disease. Among these periodontopathic bacteria, Actinobacillus actinomycetemcomitans has been implicated as an etiological agent in juvenile and adult periodontitis. Localized juvenile periodontitis is characterized by alveolar bone loss mainly affecting the permanent first molars and incisors. It is known that bone resorption is associated with the generation and activation of osteoclasts, unique bone resorbing multinucleated cells. Osteoclasts are derived from the hematopoietic progenitors, and cytokines such as interleukin-1 (IL-1) and prostaglandins (PGs) can modulate osteoclastogenesis. In this regard, we have previously shown that lipopolysaccharide (LPS) and capsular polysaccharide from A. actinomycetemcomitans are likely to play mediative roles in the induction of alveolar bone-loss in periodontal diseases.Bone morphogenetic protein-2 (BMP-2) is a member of the transforming growth factor beta superfamily. While BMP-2 is capable of inducing bone formation ectopically, little is known about its role on osteoclastogenesis. We examined the effect of BMP-2 on osteoclast-like multinucleated cell (OCL) formation in cocultures of osteoblast-like cells and hematopoietic cells of bone marrow origin. BMP-2 strongly enhanced OCL formation in a dose-dependent fashion in the presence of IL-1α. Our findings indicated that BMP-2 may enhance bone resorption instead of bone formation in inflammatory environments, suggesting that the control of inflammatory reaction in the target tissues may be one of the critical steps in clinical application of BMPs.