| First Author | Keller B | Year | 2011 |
| Journal | PLoS One | Volume | 6 |
| Issue | 1 | Pages | e16421 |
| PubMed ID | 21297990 | Mgi Jnum | J:180944 |
| Mgi Id | MGI:5308192 | Doi | 10.1371/journal.pone.0016421 |
| Citation | Keller B, et al. (2011) Interaction of TGFbeta and BMP signaling pathways during chondrogenesis. PLoS One 6(1):e16421 |
| abstractText | TGFbeta and BMP signaling pathways exhibit antagonistic activities during the development of many tissues. Although the crosstalk between BMP and TGFbeta signaling pathways is well established in bone development, the relationship between these two pathways is less well defined during cartilage development and postnatal homeostasis. We generated hypomorphic mouse models of cartilage-specific loss of BMP and TGFbeta signaling to assess the interaction of these pathways in postnatal growth plate homeostasis. We further used the chondrogenic ATDC5 cell line to test effects of BMP and TGFbeta signaling on each other's downstream targets. We found that conditional deletion of Smad1 in chondrocytes resulted in a shortening of the growth plate. The addition of Smad5 haploinsufficiency led to a more severe phenotype with shorter prehypertrophic and hypertrophic zones and decreased chondrocyte proliferation. The opposite growth plate phenotype was observed in a transgenic mouse model of decreased chondrocytic TGFbeta signaling that was generated by expressing a dominant negative form of the TGFbeta receptor I (DeltaTbetaRI) in cartilage. Histological analysis demonstrated elongated growth plates with enhanced Ihh expression, as well as an increased proliferation rate with altered production of extracellular matrix components. In contrast, in chondrogenic ATDC5 cells, TGFbeta was able to enhance BMP signaling, while BMP2 significantly reduces levels of TGF signaling. In summary, our data demonstrate that during endochondral ossification, BMP and TGFbeta signaling can have antagonistic effects on chondrocyte proliferation and differentiation in vivo. We also found evidence of direct interaction between the two signaling pathways in a cell model of chondrogenesis in vitro. |
