title: Class A scavenger receptor promotes osteoclast differentiation via the enhanced expression of receptor activator of NF-kappaB (RANK).
abstract: 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.
authors.affiliation: Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Takemura
authors.forename: Naomi
authors.initials: N
authors.lastname: Sakashita
authors.forename: Yukio
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Komohara
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Lei
authors.forename: Koji
authors.initials: K
authors.lastname: Ohnishi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kodama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mizuta
authors.forename: Motohiro
authors.initials: M
authors.lastname: Takeya
mesh_terms: D000818:Animals; D016723:Bone Remodeling; D002454:Cell Differentiation; D051379:Mice; D008817:Mice, Mutant Strains; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000096:biosynthesis* / Q000235:genetics; D051117:Scavenger Receptors, Class A / Q000235:genetics / Q000378:metabolism*
chemical_list: D053246:Receptor Activator of Nuclear Factor-kappa B; D051117:Scavenger Receptors, Class A