Analysis and characterization of the functional TGFβ receptors required for BMP6-induced osteogenic differentiation of mesenchymal progenitor cells
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Although BMP6 is highly capable of inducing osteogenic differentiation of mesenchymal progenitor cells (MPCs), the molecular mechanism involved remains to be fully elucidated. Using dominant negative (dn) mutant form of type I and type II TGFβ receptors, we demonstrated that three dn-type I receptors (dnALK2, dnALK3, dnALK6), and three dn-type II receptors (dnBMPRII, dnActRII, dnActRIIB), effectively diminished BMP6-induced osteogenic differentiation of MPCs. These findings suggested that ALK2, ALK3, ALK6, BMPRII, ActRII and ActRIIB are essential for BMP6-induced osteogenic differentiation of MPCs. However, MPCs in this study do not express ActRIIB. Moreover, RNA interference of ALK2, ALK3, ALK6, BMPRII and ActRII inhibited BMP6-induced osteogenic differentiation in MPCs. Our results strongly suggested that BMP6-induced osteogenic differentiation of MPCs is mediated by its functional TGFβ receptors including ALK2, ALK3, ALK6, BMPRII, and ActRII.
Abstract
Although BMP6 is highly capable of inducing osteogenic differentiation of mesenchymal progenitor cells (MPCs), the molecular mechanism involved remains to be fully elucidated. Using dominant negative (dn) mutant form of type I and type II TGFβ receptors, we demonstrated that three dn-type I receptors (dnALK2, dnALK3, dnALK6), and three dn-type II receptors (dnBMPRII, dnActRII, dnActRIIB), effectively diminished BMP6-induced osteogenic differentiation of MPCs. These findings suggested that ALK2, ALK3, ALK6, BMPRII, ActRII and ActRIIB are essential for BMP6-induced osteogenic differentiation of MPCs. However, MPCs in this study do not express ActRIIB. Moreover, RNA interference of ALK2, ALK3, ALK6, BMPRII and ActRII inhibited BMP6-induced osteogenic differentiation in MPCs. Our results strongly suggested that BMP6-induced osteogenic differentiation of MPCs is mediated by its functional TGFβ receptors including ALK2, ALK3, ALK6, BMPRII, and ActRII.
참고문헌 (27)
- Pittenger, M. F., "Multilineage potential of adult human mesenchymal stem cells", Science, 284, pp.143~147 (1999)
- Chen, D., "Bone morphogenetic proteins", Growth Factors, 22, pp.233~241 (2004)
- Bostrom, M. P., "Potential role of bone morphogenetic proteins in fracture healing", Clin. Orthop. Relat. Res, 355, pp.S274~S282 (1998)
- Gitelman, S. E., "Recombinant Vgr-1", BMP-6-expressing tumors induce fibrosis and enchondral bone formation in vivo, 1994, pp.126, 1595~1609
- Luu, H. H., "Distinct roles of bone morphogenetic proteins in osteogenic differentiation of mesenchymal stem cells", J. Orthop. Res, 25, pp.665~677 (2007)
- Miyazono, K., "BMP receptor signaling: transcriptional targets, regulation of signals, and signaling cross-talk", Cytokine Growth Factor Rev, 16, pp.251~263 (2005)
- Sieber, C., "Recent advances in BMP receptor signaling", Cytokine Growth Factor Rev, 20, pp.343~355 (2009)
- Ten, D. P., "Controlling cell fate by bone morphogenetic protein receptors", Mol. Cell Endocrinol, 211, pp.105~113 (2003)
- Luo, J., "TGFbeta", BMP type I receptors ALK1 and ALK2 are essential for BMP9-induced osteogenic signaling in mesenchymal stem cells, 2010, pp.285, 29588~29598
- Wu, N., "Identification and analysis of type II TGF-{beta} receptors in BMP-9-induced osteogenic differentiation of C3H10T1", 2 mesenchymal stem cells, 2010, pp.42, 699~708
- Zhao, M., "The zinc finger transcription factor Gli2 mediates bone morphogenetic protein 2 expression in osteoblasts in response to hedgehog signaling", Mol. Cell Biol, 26, pp.6197~6208 (2006)
- Lyons, K. M., "Patterns of expression of murine Vgr-1 and BMP-2 RNA suggest that transforming growth factor-β-like genes coordinately regulate aspects of embryonic development", Genes Dev, 3, pp.1657~1668 (1989)
- Celeste, A. J., "Identification of transforming growth factor-β family members present in bone-inductive protein purified from bovine bone", Proc. Nat. Acad. Sci. U.S.A, 86, pp.9843~9847 (1990)
- Slobodan, V., "BMP-6 and mesenchymal stem cell differentiation", Cytokine Growth Factor Rev, 20, pp.441~448 (2009)
- Ten Dijke, P., "Controlling cell fate by bone morphogenetic protein receptors", Mol. Cell Endocrinol, 211, pp.105~113 (2003)
- Wu, C. J., "Smad signal pathway in BMP-2-induced osteogenesis-a mini review", J. Dent. Sci, 3, pp.13~21 (2008)
- Dao-jing Xu, "Smads, p38 and ERK1", 2 are involved in BMP9-induced osteogenic differentiation of C3H10T1, BMB Reports, pp.2012, 45(4)[DOI]
- Lavery, K., "BMP-2", 4 and BMP-6, J. Biol. Chem, pp.2008, 283[DOI]
- Cao, X., "The BMP signaling and in vivo bone formation", Gene, 357, pp.1~8 (2005)
- Yamamoto, H., "Adenovirus-mediated transfer of a truncated transforming growth factor-beta (TGF-beta) type II receptor completely and specifically abolishes diverse signaling by TGF-beta in vascular wall cells in primary culture", J. Biol. Chem, 271, pp.16253~16259 (1996)
- Choi, M. E., "Inhibition of capillary morphogenesis and associated apoptosis by dominant negative mutant transforming growth factor-beta receptors", J. Biol. Chem, 270, pp.21144~21150 (1995)
- Goumans, M. J., "Activin receptor-like kinase (ALK)1 is an antagonistic mediator of lateral TGFb", ALK5 signaling, 2003, pp.12, 817~828
- Corinne, B., "Role of type I receptors for anti- Mullerian hormone in the SMAT-1 sertoli cell line", Oncogen, 24, pp.4984~4992 (2005)
- Chan, M. C., "A novel regulatory mechanism of the bone morphogenetic protein (BMP) signaling pathway involving the carboxyl-terminal tail domain of BMP type II receptor", Mol. Cell Biol, 27, pp.5776~5789 (2007)
- Mazerbourg, S., "Identification of receptors and signaling pathways for orphan bone morphogenetic protein", growth differentiation factor ligands based on genomic analyses, 2005, pp.280, 32122~32132
- Ebisawa, T., "Characterization of bone morphogenetic protein-6 signaling pathways in osteoblast differentiation", J. Cell Sci, 112, pp.3519~3527 (1999)
- Peister, A., "Adult stem cells from bone marrow (MSCs) isolated from different strains of inbred mice vary in surface epitopes, rates of proliferation, and differentiation potential", Blood, 103, pp.1662~1668 (2004)
