所属 埼玉医科大学 医学部 国際医療センター 皮膚科（皮膚腫瘍科） 職種 助教
|Class A scavenger receptor promotes osteoclast differentiation via the enhanced expression of receptor activator of NF-kappa B (RANK)
|正式名：BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
|ACADEMIC PRESS INC ELSEVIER SCIENCE
|Kenichi Takemura,Naomi Sakashita,Yukio Fujiwara,Yoshihiro Komohara,XiaoFeng Lei,Koji Ohnishi,Hiroshi Suzuki,Tatsuhiko Kodama,Hiroshi Mizuta,Motohiro Takeya
|Osteoclasts originate from bone marrow monocyte/macrophage lineage cells, and their differentiation depends on macrophage colony-stimulating factor (M-CSF) and receptor activator nuclear factor kappa B (RANK) ligand. Class A scavenger receptor (SR-A) is one of the principal functional molecules of macrophages, and its level of expression declines during osteoclast differentiation. To investigate the role of SR-A in osteoclastogenesis, we examined pathological changes in femoral bone and the expression levels of osteoclastogenesis-related molecules in SR-A(-/-) mice. The femoral osseous density of SR-A(-/-) mice was higher than that of SR-A(+/+) mice, and the number of multinucleated osteoclasts was significantly decreased. An in vitro differentiation assay revealed that the differentiation of multinucleated osteoclasts from bone marrow-derived progenitor cells is impaired in SR-A(-/-) mice. Elimination of SR-A did not alter the expression level of the M-CSF receptor, c-fins; however, the expression levels of RANK and RANK-related osteoclast-differentiation molecules such as nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1) and microphthalmia-associated transcription factor (MITF) significantly decreased. Furthermore, acetylated low-density lipoprotein (AcLDL), an SR-A ligand, significantly increased the expression level of RANK and MITF during osteoclast differentiation. These data indicate that SR-A promotes osteoclastogenesis via augmentation of the expression level of RANK and its related molecules. (C) 2009 Elsevier Inc. All rights reserved.