Tetraspanin CD9 regulates osteoclastogenesis via regulation of p44/42 MAPK activity.
Tetraspanin CD9 has been shown to regulate cell-cell fusion in sperm-egg fusion and myotube formation. However, the role of CD9 in osteoclast, another multinucleated cell type, is not still clear. Therefore, we investigated the role of CD9 in osteoclast differentiation. CD9 was expressed in osteoclast lineage cells and its expression level increased during the progression of RANKL-induced osteoclastogenesis. KMC8, a neutralizing antibody specific to CD9, significantly suppressed RANKL-induced multinucleated osteoclast formation and the mRNA expression of osteoclast differentiation marker genes. To define CD9-regulated osteoclastogenic signaling pathway, MAPK pathways were examined. KMC8 induced long-term phosphorylation of p44/42 MAPK, but not of p38 MAPK. Constitutive activation of p44/42 MAPK by overexpressing constitutive-active mutant of MEK1 almost completely blocked osteoclast differentiation. Taken together, these results suggest that CD9 expressed on osteoclast lineage cells might positively regulate osteoclastogenesis via the regulation of p44/42 MAPK activity.
Yi
Tacghee
T
Department of Cell and Developmental Biology, School of Dentistry and Dental Research Institute, Seoul National University, Republic of Korea.
Kim
Hye-Jin
HJ
Cho
Je-Yoel
JY
Woo
Kyung Mi
KM
Ryoo
Hyun-Mo
HM
Kim
Gwan-Shik
GS
Baek
Jeong-Hwa
JH
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D004789:Enzyme Activation; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism*; D060245:Tetraspanin 29
D015703:Antigens, CD; C554870:Cd9 protein, mouse; D008562:Membrane Glycoproteins; D060245:Tetraspanin 29; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3