CCR1 chemokines promote the chemotactic recruitment, RANKL development, and motility of osteoclasts and are induced by inflammatory cytokines in osteoblasts.

摘要: Chemoattractants that recruit OC precursors to locally inflamed sites of resorption are not well known. A chemokine receptor, CCR1, was expressed in and elevated mature OCs, its ligands promoted precursor recruitment, RANKL development, motility. Cytokines induced OB release such chemokines, which may therefore significantly contribute inflammatory bone loss. Introduction: Chemokines, primarily two major (CXC, CC) families, essential signals for the trafficking localization circulating hematopoietic cells into tissues. However, little is known about their potential roles osteoclast (OC) or function. Previously, we analyzed CXC receptors murine found high expression CXCR4 mediated stromal-derived factor-1(SDF-1)-induced chemotaxis collagen invasion. Here, investigated if CC ligands, other osteolytic diseases, also play important formation, activity bone-resorptive OCs. Materials Methods: receptor (CCR) mRNA during formation by RAW 264.7 primary marrow cells. Corresponding chemokines were tested ability elicit influence motility, resorption, adhesion, survival RANKL-differentiated OCs. Constitutive cytokine-induced macrophage protein-1α (MIP-1α) regulated on activation, normal T-cell secreted (RANTES) measured ELISA osteoblasts (OBs), cells. Results: CCR1 cells, most prominent CCR upregulated Chemokines bind (MIP-1α, RANTES, monocyte chemoattractant protein-3 [MCP-3]) produced varying degrees OBs, precursors, markedly increased interleukin (IL)-1α TNFα differentiating OBs. especially MIP-1α, but did alter activity, survival. All three stimulated cell leading greater OCs (in number size) after development chemoattracted directly dramatically enhanced cultures, through a pathway dependent presence without altering RANK expression. Conclusions: Pathological increases secretion these from activated OBs potently stimulate chemotactic recruitment thereby exacerbating local osteolysis multiple skeletal diseases.