腎と骨代謝 Vol.21 No.1(3)


特集名 骨と免疫
題名 Toll様受容体による破骨細胞の分化調節
発刊年月 2008年 01月
著者 高見 正道 昭和大学歯学部口腔生化学教室
著者 超 宝紅 昭和大学歯学部口腔生化学教室
【 要旨 】 Toll様受容体 (Toll-like receptor ; TLR) は，細菌やウイルスの構成成分を認識し，炎症を誘発する一群の膜蛋白質である．破骨細胞の分化初期ではTLR刺激が分化を抑制するが，分化後期ではRANKLと同様に分化を誘導する．また，成熟破骨細胞のアポトーシスを抑制する機能をもつ．一方，骨芽細胞もTLRを発現しており，TLRからのシグナルはRANKLとOPGの発現を調節する．さらに，TLRはTNF-αやプロスタグランジンE2の産生を誘導し，破骨細胞分化を間接的に促進することが示唆されている．
Theme Osteoimmunology
Title Regulation of osteoclast differentiation by Toll-like receptors
Author Masamichi Takami Department of Biochemistry, School of Dentistry, Showa University
Author Baohong Zhao Department of Biochemistry, School of Dentistry, Showa University
[ Summary ] Toll-like receptors (TLRs) are membrane-type proteins that recognize a range of microbial constituents such as lipopolysaccharide (LPS) and nucleotides released from invading bacteria and viruses, triggering inflammation. In the early stages of osteoclast differentiation, activation of TLRs inhibits osteoclast differentiation. However, activation of TLRs induces osteoclast differentiation in the late differentiation stage. Activation of TLRs also helps mature osteoclasts survive by blocking apoptosis. On the other hand, TLRs expressed in osteoblasts induce the expression of RANKL, which in turn induces osteoclast differentiation. It is highly probable that osteoclast differentiation is promoted by the production of inflammatory factors such as TNF-α and PGE2.
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