Role of intercellular adhesion molecule-2 in osteoclastogenesis.
Osteoclasts, multinucleated bone-resorbing cells, are specialized cells derived from the monocyte/macrophage lineage. Therefore, it is essential for mononuclear precursors to find a fusion partner during its differentiation. Our previous study showed an important role of cell communication via Mac-1 (CD11b/CD18) during osteoclastogenesis. However, the counter receptor of Mac-1 was still unknown. Flow cytometric analysis showed that bone marrow-derived mononuclear cells, used as osteoclast precursors, expressed intercellular adhesion molecule-1 and -2. Quantitative RT-PCR analysis revealed that expression level of ICAM-2 was higher than that of ICAM-1 in bone marrow cells. The osteoclastogenesis induced by receptor activator of NF-kappaB ligand (RANKL) was inhibited by anti-ICAM-2 neutralizing antibody but not by anti-ICAM-1 neutralizing antibody. The inhibitory effect of anti-ICAM-2 antibody on osteoclastogenesis was enhanced by simultaneous treatment of anti-CD11b neutralizing antibody. Furthermore, osteoclastogenesis induced by tumor necrosis factor α (TNFα) was also inhibited by anti-ICAM-2 neutralizing antibody. The involvement of lymphocytes in osteoclastogenesis was excluded, because anti-ICAM-2 antibody inhibited osteoclastogenesis using bone marrow-derived cells from immunodeficiency mice. Immunocytochemical staining demonstrated colocalization of ICAM-2 and Mac-1 during osteoclastogenesis; however, Mac-1 immunoreactivity was lost in differentiated multinucleated osteoclast. These results suggest the important role of ICAM-2/Mac-1 binding in osteoclastogenesis induced by either RANKL or TNFα.
Department of Cellular Physiological Chemistry, Graduate School, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8549, Japan.
Xianglan
X
Li
Masako
M
Akiyama
Ken-ichi
K
Nakahama
Taro
T
Koshiishi
Satoru
S
Takeda
Ikuo
I
Morita
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D001402:B-Lymphocytes / Q000378:metabolism; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D015870:Gene Expression; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008297:Male; D051379:Mice; D016513:Mice, SCID; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism*; D010014:Osteolysis / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D053245:RANK Ligand / Q000494:pharmacology; D013601:T-Lymphocytes / Q000378:metabolism
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; C480027:ICAM-2 protein, mouse; D016177:Macrophage-1 Antigen; D053245:RANK Ligand; D018799:Intercellular Adhesion Molecule-1