SDF-1 increases recruitment of osteoclast precursors by upregulation of matrix metalloproteinase-9 activity.
Although chemokines play essential roles in the trafficking and homing of many circulating hematopoietic cell types, their potential influences on osteoclast (OC) recruitment or bone remodeling are not well known. Therefore, chemokine receptor expression was analyzed by RNase protection assay during OC formation induced by RANKL in a murine mononuclear cell line (RAW 264.7). Relatively high CXCR4 expression was detected in RAW cells (pre-OCs), whereas CXCR4 levels were downregulated during RAW-OC development. SDF-1, the unique ligand for CXCR4, stimulated RAW cell production of matrix metalloproteinase (MMP)-9 activity, a matrix-degrading enzyme essential for pre-OC migration into the developing bone marrow cavity. Induced MMP-9 activity in RAW cells was associated with their increased MMP-dependent transmigration through a collagen gel in response to SDF-1. We conclude that SDF-1 stimulation of MMP-9 activity in pre-OCs may be a key aspect of their recruitment to bone and migration within the marrow to sites for OC differentiation and bone resorption.
Yu
Xuefeng
X
Department of Biology, Washington University, St. Louis, Missouri 63130, USA.
Collin-Osdoby
Patricia
P
Osdoby
Philip
P
D000818:Animals; D002352:Carrier Proteins / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology*; D008264:Macrophages; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D008562:Membrane Glycoproteins / Q000494:pharmacology; D051379:Mice; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D053245:RANK Ligand; D012333:RNA, Messenger / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B; D019718:Receptors, CXCR4 / Q000096:biosynthesis / Q000235:genetics; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D015854:Up-Regulation
D002352:Carrier Proteins; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D012333:RNA, Messenger; D053246:Receptor Activator of Nuclear Factor-kappa B; D019718:Receptors, CXCR4; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D020780:Matrix Metalloproteinase 9