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Differential Roles for Bone Morphogenetic Protein (BMP) Receptor Type IB and IA in Differentiation and Specification of Mesenchymal Precursor Cells to Osteoblast and Adipocyte Lineages
Open accessAbstract
Cumulative evidence indicates that osteoblasts and adipocytes share a common mesenchymal precursor and that bone morphogenetic proteins (BMPs) can induce both osteoblast and adipocyte differentiation of this precursor. In the present study, we investigated the roles of BMP receptors in differentiation along these separate lineages using a well-characterized clonal cell line, 2T3, derived from the mouse calvariae. BMP-2 induced 2T3 cells to differentiate into mature osteoblasts or adipocytes depending upon culture conditions. To test the specific roles of the type IA and IB BMP receptor components, truncated and constitutively active type IA and IB BMP receptor cDNAs were stably expressed in these cells. Overexpression of truncated type IB BMP receptor (trBMPR-IB) in 2T3 cells completely blocked BMP-2–induced osteoblast differentiation and mineralized bone matrix formation. Expression of trBMPR-IB also blocked mRNA expression of the osteoblast specific transcription factor, Osf2/ Cbfa1, and the osteoblast differentiation-related genes, alkaline phosphatase (ALP) and osteocalcin (OC). BMP-2–induced ALP activity could be rescued by transfection of wild-type (wt) BMPR-IB into 2T3 clones containing trBMPR-IB. Expression of a constitutively active BMPR-IB (caBMPR-IB) induced formation of mineralized bone matrix by 2T3 cells without addition of BMP-2. In contrast, overexpression of trBMPR-IA blocked adipocyte differentiation and expression of caBMPR-IA induced adipocyte formation in 2T3 cells. Expression of the adipocyte differentiation-related genes, adipsin and PPARγ, correlated with the distinct phenotypic changes found after overexpression of the appropriate mutant receptors. These results demonstrate that type IB and IA BMP receptors transmit different signals to bone-derived mesenchymal progenitors and play critical roles in both the specification and differentiation of osteoblasts and adipocytes.
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Cites
Osf2/Cbfa1: A Transcriptional Activator of Osteoblast Differentiation
Ducy, P., Zhang, R., Geoffroy, V., Ridall, A. L., & Karsenty, G. (1997) · Cell · doi:10.1016/s0092-8674(00)80257-3 · Cited by 4,246
Self-citationLehmann, J. M., Lenhard, J. M., Oliver, B. B., Ringold, G. M., & Kliewer, S. A. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.6.3406 · Cited by 1,110
Cited by
SPECIFICITY AND VERSATILITY IN TGF-β SIGNALING THROUGH SMADS
Feng, X.-H., & Derynck, R. (2005) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.21.022404.142018 · Cited by 1,869
A Review of the Clinical Side Effects of Bone Morphogenetic Protein-2
James, A. W., LaChaud, G., Shen, J., Asatrian, G., Nguyen, V., Zhang, X., Ting, K., & Soo, C. (2016) · Tissue Engineering Part B: Reviews · doi:10.1089/ten.teb.2015.0357 · Cited by 1,131
Atashi, F., Modarressi, A., & Pepper, M. S. (2015) · Stem Cells and Development · doi:10.1089/scd.2014.0484 · Cited by 603
Alliston, T., Choy, L., Ducy, P., Karsenty, G., & Derynck, R. (2001) · The EMBO Journal · doi:10.1093/emboj/20.9.2254 · Cited by 526
Self-citationHalvorsen, Y.-D. C., Franklin, D., Bond, A. L., Hitt, D. C., Auchter, C., Boskey, A. L., Paschalis, E. P., Wilkison, W. O., & Gimble, J. M. (2001) · Tissue Engineering · doi:10.1089/107632701753337681 · Cited by 508
Metadata
- Authors
- Chen, D., Ji, X., Harris, M. A., Feng, J. Q., Karsenty, G., Celeste, A. J., Rosen, V., Mundy, G. R., & Harris, S. E.
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 1998-07-13
- Volume
- 142
- Issue
- 1
- Pages
- 295-305
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- OpenAlex
- W2012295730
- Cited by
- 382
- References
- 2
- FWCI
- 5.52
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: Differential Roles for Bone Morphogenetic Protein (BMP) Receptor Type IB and IA in Differentiation and Specification of Mesenchymal Precursor Cells to Osteoblast and Adipocyte Lineages. https://app.cochat.ai/papers/10.1083/jcb.142.1.295
- The paper
- Chen, D., Ji, X., Harris, M. A., Feng, J. Q., Karsenty, G., Celeste, A. J., Rosen, V., Mundy, G. R., & Harris, S. E. (1998). Differential Roles for Bone Morphogenetic Protein (BMP) Receptor Type IB and IA in Differentiation and Specification of Mesenchymal Precursor Cells to Osteoblast and Adipocyte Lineages. The Journal of Cell Biology. https://doi.org/10.1083/jcb.142.1.295
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.