MCP-1 expressed by osteoclasts stimulates osteoclastogenesis in an autocrine/paracrine manner.
Monocyte chemoattractant protein-1 (MCP-1) is a chemokine that plays a critical role in the recruitment and activation of leukocytes. Here, we describe that multinuclear osteoclast formation was significantly inhibited in cells derived from MCP-1-deficient mice. MCP-1 has been implicated in the regulation of osteoclast cell-cell fusion; however defects of multinuclear osteoclast formation in the cells from mice deficient in DC-STAMP, a seven transmembrane receptor essential for osteoclast cell-cell fusion, was not rescued by recombinant MCP-1. The lack of MCP-1 in osteoclasts resulted in a down-regulation of DC-STAMP, NFATc1, and cathepsin K, all of which were highly expressed in normal osteoclasts, suggesting that osteoclast differentiation was inhibited in MCP-1-deficient cells. MCP-1 alone did not induce osteoclastogenesis, however, the inhibition of osteoclastogenesis in MCP-1-deficient cells was restored by addition of recombinant MCP-1, indicating that osteoclastogenesis was regulated in an autocrine/paracrine manner by MCP-1 under the stimulation of RANKL in osteoclasts.
Department of Orthopedic Surgery, Keio University School of Medicine, Shinano-machi, Shinjuku-ku, Tokyo, Japan.
Kana
K
Miyamoto
Ken
K
Ninomiya
Koh-Hei
KH
Sonoda
Yoshiteru
Y
Miyauchi
Hiroko
H
Hoshi
Ryotaro
R
Iwasaki
Hiroya
H
Miyamoto
Shigeyuki
S
Yoshida
Yuiko
Y
Sato
Hideo
H
Morioka
Kazuhiro
K
Chiba
Kensuke
K
Egashira
Toshio
T
Suda
Yoshiaki
Y
Toyama
Takeshi
T
Miyamoto
D000818:Animals; D019898:Autocrine Communication; D002454:Cell Differentiation / Q000235:genetics; D002459:Cell Fusion; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism / Q000502:physiology*; D053245:RANK Ligand / Q000378:metabolism
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; C499636:DC-STAMP protein, mouse; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse