Analysis and characterization of the functional TGFβ receptors required for BMP6-induced osteogenic differentiation of mesenchymal progenitor cells = Analysis and characterization of the functional TGFβ receptors required for BMP6-induced osteogenic differentiation of mesenchymal progenitor cells

다국어 초록 (Multilingual 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. [BMB Reports 2013; 46(2): 107-112].

참고문헌 (Reference)

1 Zhao, M., "The zinc finger transcription factor Gli2 mediates bone morphogenetic protein 2 expression in osteoblasts in response to hedgehog signaling" 26 : 6197-6208, 2006

2 Cao, X., "The BMP signaling and in vivo bone formation" 357 : 1-8, 2005

3 Luo, J., "TGFbeta/BMP type I receptors ALK1 and ALK2 are essential for BMP9-induced osteogenic signaling in mesenchymal stem cells" 285 : 29588-29598, 2010

4 Dao-jing Xu, "Smads, p38 and ERK1/2 are involved in BMP9-induced osteogenic differentiation of C3H10T1/2 mesenchymal stem cells" 생화학분자생물학회 45 (45): 247-252, 2012

5 Wu, C. J., "Smad signal pathway in BMP-2-induced osteogenesis-a mini review" 3 : 13-21, 2008

6 Corinne, B., "Role of type I receptors for anti- Mullerian hormone in the SMAT-1 sertoli cell line" 24 : 4984-4992, 2005

7 Gitelman, S. E., "Recombinant Vgr-1/BMP-6-expressing tumors induce fibrosis and enchondral bone formation in vivo" 126 : 1595-1609, 1994

8 Sieber, C., "Recent advances in BMP receptor signaling" 20 : 343-355, 2009

9 Bostrom, M. P., "Potential role of bone morphogenetic proteins in fracture healing" 355 : S274-S282, 1998

10 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" 3 : 1657-1668, 1989

11 Pittenger, M. F., "Multilineage potential of adult human mesenchymal stem cells" 284 : 143-147, 1999

12 Choi, M. E., "Inhibition of capillary morphogenesis and associated apoptosis by dominant negative mutant transforming growth factor-beta receptors" 270 : 21144-21150, 1995

13 Celeste, A. J., "Identification of transforming growth factor-β family members present in bone-inductive protein purified from bovine bone" 86 : 9843-9847, 1990

14 Mazerbourg, S., "Identification of receptors and signaling pathways for orphan bone morphogenetic protein/growth differentiation factor ligands based on genomic analyses" 280 : 32122-32132, 2005

15 Wu, N., "Identification and analysis of type II TGF-{beta} receptors in BMP-9-induced osteogenic differentiation of C3H10T1/2 mesenchymal stem cells" 42 : 699-708, 2010

16 Luu, H. H., "Distinct roles of bone morphogenetic proteins in osteogenic differentiation of mesenchymal stem cells" 25 : 665-677, 2007

17 Ten Dijke, P., "Controlling cell fate by bone morphogenetic protein receptors" 211 : 105-113, 2003

18 Ten, D. P., "Controlling cell fate by bone morphogenetic protein receptors" 211 : 105-113, 2003

19 Ebisawa, T., "Characterization of bone morphogenetic protein-6 signaling pathways in osteoblast differentiation" 112 : 3519-3527, 1999

20 Chen, D., "Bone morphogenetic proteins" 22 : 233-241, 2004

21 Slobodan, V., "BMP-6 and mesenchymal stem cell differentiation" 20 : 441-448, 2009

22 Lavery, K., "BMP-2/4 and BMP-6/7 differentially utilize cell surface receptors to induce osteoblastic differentiation of human bone marrow-derived mesenchymal stem cells" 283 : 20948-20958, 2008

23 Miyazono, K., "BMP receptor signaling: transcriptional targets, regulation of signals, and signaling cross-talk" 16 : 251-263, 2005

24 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" 103 : 1662-1668, 2004

25 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" 271 : 16253-16259, 1996

26 Goumans, M. J., "Activin receptor-like kinase (ALK)1 is an antagonistic mediator of lateral TGFb/ALK5 signaling" 12 : 817-828, 2003

27 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" 27 : 5776-5789, 2007