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Publication : Class A scavenger receptor promotes osteoclast differentiation via the enhanced expression of receptor activator of NF-kappaB (RANK).

First Author  Takemura K Year  2010
Journal  Biochem Biophys Res Commun Volume  391
Issue  4 Pages  1675-80
PubMed ID  20036645 Mgi Jnum  J:157090
Mgi Id  MGI:4430005 Doi  10.1016/j.bbrc.2009.12.126
Citation  Takemura K, et al. (2010) Class A scavenger receptor promotes osteoclast differentiation via the enhanced expression of receptor activator of NF-kappaB (RANK). Biochem Biophys Res Commun 391(4):1675-80
abstractText  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-fms; 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.
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