Premium
Absence of MCP‐1 leads to elevated bone mass via impaired actin ring formation
Author(s) -
Sul OkJoo,
Ke Ke,
Kim WoonKi,
Kim SongHee,
Lee SangChul,
Kim HyunJu,
Kim ShinYoon,
Suh JaeHee,
Choi HyeSeon
Publication year - 2012
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.22879
Subject(s) - osteoclast , chemistry , bone resorption , endocrinology , bone remodeling , medicine , receptor , stimulation , resorption , bone marrow , knockout mouse , microbiology and biotechnology , biology
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. J. Cell. Physiol. 227: 1619–1627, 2012. © 2011 Wiley Periodicals, Inc.