Class A scavenger receptor promotes osteoclast differentiation via the enhanced expression of receptor activator of NF-kappaB (RANK).
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.
Takemura
Kenichi
K
Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
Sakashita
Naomi
N
Fujiwara
Yukio
Y
Komohara
Yoshihiro
Y
Lei
Xiaofeng
X
Ohnishi
Koji
K
Suzuki
Hiroshi
H
Kodama
Tatsuhiko
T
Mizuta
Hiroshi
H
Takeya
Motohiro
M
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*
D053246:Receptor Activator of Nuclear Factor-kappa B; D051117:Scavenger Receptors, Class A