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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2017.5
- 수록면
- 371 - 377 (7page)
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Despite the importance of the receptor activator of nuclear factor (NF)-kappaB ligand (RANKL)-RANK signaling mechanisms on osteoclast differentiation, little has been studied on how RANK expression is regulated or what regulates its expression during osteoclastogenesis. We show here that insulin signaling increases RANK expression, thus enhancing osteoclast differentiation by RANKL. Insulin stimulation induced RANK gene expression in time- and dose-dependent manners and insulin receptor shRNA completely abolished RANK ex-pression induced by insulin in bone marrow-derived monocyte/macrophage cells (BMMs). Moreover, the addi-tion of insulin in the presence of RANKL promoted RANK expression. The ability of insulin to regulate RANK expression depends on extracellular signal-regulated kinase 1/2 (ERK1/2) since only PD98059, an ERK1/2 inhibitor, specifically inhibited its expression by insulin. However, the RANK expression by RANKL was blocked by all three mitogen-activated protein (MAP) kinases inhibitors. The activation of RANK increased differen-tiation of BMMs into tartrate-resistant acid phosphatase-positive (TRAP+) osteoclasts as well as the expression of dendritic cell-specific transmembrane protein (DC-STAMP) and d2 isoform of vacuolar (H+) ATPase (v-ATPase) Vo domain (Atp6v0d2), genes critical for osteoclastic cell-cell fusion. Collectively, these results suggest that insulin induces RANK expression via ERK1/2, which contributes to the enhancement of osteoclast differentiation.
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참고문헌 (37)
참고문헌 신청
Boyle, W. J. / 2003 / Osteoclast differentiation and activation / Nature 423:337~342
Choi, H. K. / 2013 / Early estrogen-induced gene 1, a novel RANK signaling component, is essential for osteoclastogenesis / Cell Res 23:524~536
Dougall, W. C. / 1999 / RANK is essential for osteoclast and lymph node development / Genes. Dev 13:2412~2424
Erbagci, A. B. / 2002 / Serum prolidase activity as a marker of osteoporosis in type 2 diabetes mellitus / Clin. Biochem 35:263~268
Ferron, M. / 2010 / Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism / Cell 142:296~308
Choi, H. K. / 2013 / Early estrogen-induced gene 1, a novel RANK signaling component, is essential for osteoclastogenesis / Cell Res 23:524~536
Dougall, W. C. / 1999 / RANK is essential for osteoclast and lymph node development / Genes. Dev 13:2412~2424
Erbagci, A. B. / 2002 / Serum prolidase activity as a marker of osteoporosis in type 2 diabetes mellitus / Clin. Biochem 35:263~268
Ferron, M. / 2010 / Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism / Cell 142:296~308
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