RIP function on osteoclastogenesis
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Bone is continuously remodeled by osteoblasts and osteoclasts. Proper balance between bone matrix formation by osteoblasts and resorption by osteoclasts is essential for proper bone metabolism and these processes are tightly regulated by various hormones and cytokines in local microenvironments. Osteoclasts are multinucleated cells that form only in bone and specialize in the resorption of calcified matrix. Osteoclasts were derive from hematopoietic cells in the bone marrow and stimulated by receptor activator of nuclear factor NF-κB ligand (TRANCE, RANKL). RIP is known as a potent therapeutic agent with anti-inflammatory by activation of T cell potential. However, the regulatory effects of RIP on osteoclast differentiation are unclear. In this study, We examined the effects of RIP on osteoclast differentiation with respect to bone resorption. RIP negatively regulates TRANCE-induced osteoclast differentiation. Expression levels of RIP are significantly reduced by TRANCE during osteoclastogenesis. Overexpression of RIP in bone marrow-derived monocyte/macrophage lineage cells (BMMs) inhibits the formation of TRAP multinuclear osteoclasts. Furthermore, overexpression of RIP in BMMs attenuates the gene induction of nuclear factor of activated T cells (NFAT) c1 and osteoclast-associated receptor (OSCAR) during TRANCE-mediated osteoclastogenesis. Taken together, our results suggest that RIP can act as an important modulator of TRANCE-mediated osteoclastogenesis.
Abstract
Bone is continuously remodeled by osteoblasts and osteoclasts. Proper balance between bone matrix formation by osteoblasts and resorption by osteoclasts is essential for proper bone metabolism and these processes are tightly regulated by various hormones and cytokines in local microenvironments. Osteoclasts are multinucleated cells that form only in bone and specialize in the resorption of calcified matrix. Osteoclasts were derive from hematopoietic cells in the bone marrow and stimulated by receptor activator of nuclear factor NF-κB ligand (TRANCE, RANKL). RIP is known as a potent therapeutic agent with anti-inflammatory by activation of T cell potential. However, the regulatory effects of RIP on osteoclast differentiation are unclear. In this study, We examined the effects of RIP on osteoclast differentiation with respect to bone resorption. RIP negatively regulates TRANCE-induced osteoclast differentiation. Expression levels of RIP are significantly reduced by TRANCE during osteoclastogenesis. Overexpression of RIP in bone marrow-derived monocyte/macrophage lineage cells (BMMs) inhibits the formation of TRAP multinuclear osteoclasts. Furthermore, overexpression of RIP in BMMs attenuates the gene induction of nuclear factor of activated T cells (NFAT) c1 and osteoclast-associated receptor (OSCAR) during TRANCE-mediated osteoclastogenesis. Taken together, our results suggest that RIP can act as an important modulator of TRANCE-mediated osteoclastogenesis.
참고문헌 (11)
- W. J. Boyle, "Osteoclast differentiation and activation", Nature, 423, pp.337~342 (2000)
- H. Takayanagi, "Osteoimmunology : shared mechanisms and crosstalk between the immune and cone systems", Nature Reviews Immunology, 7, pp.292~304 (2007)
- H. Yasuda, "Osteoclast differentiation factor is a ligand for osteoprotegerin", osteoclastogenesis -inhibitory factor and is identical to TRANCE, Proc. Natl. Acad. Sci. U. S. A, pp.1998, 95[DOI]
- B. F. Boyce, "Roles for NF-kappaB and c-Fos in osteoclasts", Journal of Bone and Mineral Metabolism, 23, pp.11~15 (2005)
- T. Koga, "Costimulatory signals mediated by the ITAM motif cooperate with RNAKL for bone homeostasis", Nature, 428, pp.758~763 (2004)
- H. Takayanagi, "Induction and activation of the transcriprion factor NFATc1 (NFATc2)integrate RANKL signaling in terminal differentiation of osteoclast", Developmental Cell, 3, pp.889~901 (2002)
- E. Meylan, "he RIP kinases: crucial integrators of cellular stress", TRENDS in biochemical Sciences, 30(3), pp.151~159 (2005)
- T. H. Lee, "The kinase activity of Rip1 is not required for tumor necrosis factor-a-induced IkB kinase or p38 MAP kinase activation or for the ubiquitination of Rip1 by Traf2", J. Biol. Chem, 279, pp.33185~33191 (2004)
- K. Shimada, "The NOD", RIP2pathway is essential for host defenses against Chlamydophila pneumoniae lung infection, 2009, pp.5(4), e1000379~
- L. Moreno, "Nucleotide oligomerization domain 1 is a dominant pathway for NOS2 induction in vascular smooth muscle cells: comparison with Toll-like receptor 4 responses in macrophages", Br J Pharmacol, 160(8), pp.1997~2007 (2010)
- K. Moriwaki, "Chan, RIP3:a molecular switch for necrosis and inflammation", Genes Dev, 27(15), pp.1640~1649 (2013)