Insulin enhances RANKL-induced osteoclastogenesis via ERK1/2 activation and induction of NFATc1 and Atp6v0d2.
Insulin is one of the main factors affecting bone and energy metabolism, however, the direct effect of insulin on osteoclast differentiation remains unclear. Thus, in order to help elucidate that puzzle, the authors investigated the roles and regulatory mechanisms of insulin on osteoclasts differentiation. Co-stimulation with insulin and RANKL significantly enhanced the number of larger (>100 μm) osteoclastic cells and of TRAP-positive multinucleated cells compared with treatment by RANKL alone. Conversely, the insulin receptor shRNA markedly decreased osteoclast differentiation induced by insulin and RANKL. Insulin treatment significantly activated ERK1/2 MAP kinase as well as markedly induced the expression of NFATc1, an osteoclast marker gene, and Atp6v0d2, an osteoclast fusion-related gene. The pretreatment of PD98059, an ERK1/2 inhibitor, or insulin receptor shRNA effectively suppressed osteoclast differentiation and, in addition, blocked the expression of NFATc1 and Atp6vod2 induced by insulin stimulation. These data reveal insights into the regulation of osteoclast differentiation and fusion through ERK1/2 activation and the induction of NFATc1 and Atp6v0d2 by insulin.
Department of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University, Asan-Si, Chungnam 336-745, Republic of Korea; Department of Medical Science, College of Medical Sciences, Soonchunhyang University, Asan-Si, Chungnam 336-745, Republic of Korea.
Ju Hee
JH
Oh
Department of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University, Asan-Si, Chungnam 336-745, Republic of Korea.
Jae Yoon
JY
Lee
Department of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University, Asan-Si, Chungnam 336-745, Republic of Korea.
Seung Hee
SH
Joung
Department of Medical Science, College of Medical Sciences, Soonchunhyang University, Asan-Si, Chungnam 336-745, Republic of Korea.
Yoon Taek
YT
Oh
Department of Biomedical Laboratory Science, Korea Nazarene University, Cheonan-Si, Chungnam 331-718, Republic of Korea.
Hong Sung
HS
Kim
Department of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University, Asan-Si, Chungnam 336-745, Republic of Korea; Department of Medical Science, College of Medical Sciences, Soonchunhyang University, Asan-Si, Chungnam 336-745, Republic of Korea. Electronic address: nlee@sch.ac.kr.
Na Kyung
NK
Lee
D000818:Animals; D002454:Cell Differentiation; D002459:Cell Fusion; D002478:Cells, Cultured; D004789:Enzyme Activation; D007328:Insulin / Q000502:physiology*; D020935:MAP Kinase Signaling System; D008264:Macrophages / Q000201:enzymology; D008297:Male; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D010010:Osteoclasts / Q000502:physiology*; D053245:RANK Ligand / Q000502:physiology*; D015533:Transcriptional Activation; D025262:Vacuolar Proton-Translocating ATPases / Q000096:biosynthesis / Q000235:genetics*
D007328:Insulin; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse; D019950:Mitogen-Activated Protein Kinase 1; C542312:Atp6v0d2 protein, mouse; D025262:Vacuolar Proton-Translocating ATPases
Atp6v0d2; ERK1/2; Insulin; NFATc1; Osteoclast differentiation