MKK6-p38 MAPK signaling pathway enhances survival but not bone-resorbing activity of osteoclasts.
Phosphorylated p38 mitogen-activating kinase (MAPK) is observed in osteoclasts under in vivo inflammatory situations. However, the role of p38 MAPK in osteoclast function has not been elucidated, because all external stimuli tested hitherto failed to induce the phosphorylation of p38 MAPK in osteoclasts in culture. In this study, a constitutively active form of MKK6 (MKK6CA) was expressed in osteoclasts using adenoviral gene transfer in vitro. MKK6CA expressed in osteoclasts phosphorylated p38 MAPK and enhanced the survival of osteoclasts. Dentine-resorbing activity of osteoclasts was not enhanced by the MKK6CA expression. These results suggest that p38 MAPK signaling plays a critical role in the survival of osteoclasts in inflammatory diseases.
Yamashita
Teruhito
T
Division of Hard Tissue Research, Institute for Oral Science, Matsumoto Dental University, 1780 Gobara-Hirooka, Shiojiri, Nagano 399-0871, Japan.
Kobayashi
Yasuhiro
Y
Mizoguchi
Toshihide
T
Yamaki
Mariko
M
Miura
Toshiki
T
Tanaka
Sakae
S
Udagawa
Nobuyuki
N
Takahashi
Naoyuki
N
D000818:Animals; D000831:Animals, Newborn; D001862:Bone Resorption / Q000378:metabolism*; D002470:Cell Survival; D002478:Cells, Cultured; D048669:MAP Kinase Kinase 6 / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D051379:Mice; D010010:Osteoclasts / Q000378:metabolism* / Q000473:pathology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D048051:p38 Mitogen-Activated Protein Kinases; D048669:MAP Kinase Kinase 6; C482567:Map2k6 protein, mouse