title: Absence of MCP-1 leads to elevated bone mass via impaired actin ring formation.
abstract: Monocyte chemoattractant protein-1 (MCP-1) is associated with various inflammatory diseases involving bone loss, and is expressed along with its receptor by bone marrow-derived macrophages (BMM), which are osteoclast (OC) precursors. To investigate the role of MCP-1 in bone remodeling, we compared MCP-1-knockout (KO) mice with wild-type (WT) mice. The absence of MCP-1 increased bone mass and lowered serum collagen type I fragments (CTX-1) and TRACP 5b, but had no significant effect on the N-terminal propeptide of type I procollagen, suggesting that OCs are primarily responsible for the bone phenotype observed in the absence of MCP-1. MCP-1 deficiency resulted in reduced numbers and activity of OCs in vitro. It also led to a reduced level of c-Fms and receptor activator of nuclear factor-κB receptor and impaired actin ring formation. Activation of ERK, Akt, Rac1, and Rho upon M-CSF stimulation was also reduced and our evidence suggests that the aberrant actin ring formation was partly due to reduced activation of these molecules. Our findings point to a role of osteoclast MCP-1 in regulating bone remodeling. The higher bone mass in the femurs of MCP-1-KO mice could be, at least in part, due to decreased osteoclastogenesis and bone resorption resulting from aberrant M-CSF signaling in OCs.
authors.affiliation: Department of Biological Sciences (BK21 Program) and the Immunomodulation Research Center, University of Ulsan, Ulsan, Korea.
authors.forename: Ok-Joo
authors.initials: OJ
authors.lastname: Sul
authors.forename: Ke
authors.initials: K
authors.lastname: Ke
authors.forename: Woon-Ki
authors.initials: WK
authors.lastname: Kim
authors.forename: Song-Hee
authors.initials: SH
authors.lastname: Kim
authors.forename: Sang-Chul
authors.initials: SC
authors.lastname: Lee
authors.forename: Hyun-Ju
authors.initials: HJ
authors.lastname: Kim
authors.forename: Shin-Yoon
authors.initials: SY
authors.lastname: Kim
authors.forename: Jae-Hee
authors.initials: JH
authors.lastname: Suh
authors.forename: Hye-Seon
authors.initials: HS
authors.lastname: Choi
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D016723:Bone Remodeling / Q000235:genetics / Q000502:physiology*; D001862:Bone Resorption / Q000378:metabolism / Q000473:pathology; D001842:Bone and Bones / Q000033:anatomy & histology / Q000000981:diagnostic imaging; D018932:Chemokine CCL2 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D005260:Female; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D055114:X-Ray Microtomography
chemical_list: D000199:Actins; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D017931:DNA Primers; D016173:Macrophage Colony-Stimulating Factor