| First Author | Wang W | Year | 2019 |
| Journal | Proc Natl Acad Sci U S A | Volume | 116 |
| Issue | 31 | Pages | 15570-15579 |
| PubMed ID | 31311865 | Mgi Jnum | J:278336 |
| Mgi Id | MGI:6342677 | Doi | 10.1073/pnas.1902927116 |
| Citation | Wang W, et al. (2019) The TGFbeta type I receptor TGFbetaRI functions as an inhibitor of BMP signaling in cartilage. Proc Natl Acad Sci U S A 116(31):15570-15579 |
| abstractText | The type I TGFbeta receptor TGFbetaRI (encoded by Tgfbr1) was ablated in cartilage. The resulting Tgfbr1 (Col2) mice exhibited lethal chondrodysplasia. Similar defects were not seen in mice lacking the type II TGFbeta receptor or SMADs 2 and 3, the intracellular mediators of canonical TGFbeta signaling. However, we detected elevated BMP activity in Tgfbr1 (Col2) mice. As previous studies showed that TGFbetaRI can physically interact with ACVRL1, a type I BMP receptor, we generated cartilage-specific Acvrl1 (Acvrl1 (Col2) ) and Acvrl1/Tgfbr1 (Acvrl1/Tgfbr1 (Col2) ) knockouts. Loss of ACVRL1 alone had no effect, but Acvrl1/Tgfbr1 (Col2) mice exhibited a striking reversal of the chondrodysplasia seen in Tgfbr1 (Col2) mice. Loss of TGFbetaRI led to a redistribution of the type II receptor ACTRIIB into ACVRL1/ACTRIIB complexes, which have high affinity for BMP9. Although BMP9 is not produced in cartilage, we detected BMP9 in the growth plate, most likely derived from the circulation. These findings demonstrate that the major function of TGFbetaRI in cartilage is not to transduce TGFbeta signaling, but rather to antagonize BMP signaling mediated by ACVRL1. |
