| First Author | Peters SB | Year | 2017 |
| Journal | Bone | Volume | 97 |
| Pages | 54-64 | PubMed ID | 28043895 |
| Mgi Jnum | J:255163 | Mgi Id | MGI:6112664 |
| Doi | 10.1016/j.bone.2016.12.017 | Citation | Peters SB, et al. (2017) Tgfbr2 is required in osterix expressing cells for postnatal skeletal development. Bone 97:54-64 |
| abstractText | Transforming growth factor beta (TGFbeta) is known to play an important role in early skeletal development. We previously demonstrated that loss of TGFbeta receptor II (Tgfbr2) in Prx1-Cre-expressing mesenchyme results in defects in long bones, joints, and the skull vault in mice resulting from reduced naive mesenchymal proliferation and condensation that interrupted osteoblast differentiation. In contrast, others have shown that the loss of Tgfbr2 in fully differentiated mature osteoblasts results in increased bone volume. To study the role of Tgfbr2 in immature osteoblasts, we generated Osx-Cre;Tgfbr2(fl/fl) mice and found defects in the postnatal development of the skull vault and long bones as compared to controls. No discernible skeletal defects were observed in newborn mice; however, at postnatal day 24 (P24), Tgfbr2-deleted mice demonstrated short stature that correlated with reduced proliferation in the growth plate. X-ray and microCT analysis of long bone and skull from P24 mice showed reduced bone volume. Histomorphometry indicated reductions in osteoblast number but not osteoclast number. Quantitative real-time PCR demonstrated mRNA levels for the osteoblast marker, Runx2, were not altered but mRNA levels of a marker for mature osteoblasts, Bglap, were down in mutant calvaria relative to controls. The mRNA of a proliferation marker, proliferative nuclear cell antigen (PCNA), was also reduced whereas the ratio of Bax2:Bcl2 was unaltered to demonstrate no change in apoptosis. These results suggest proliferation and maturation of immature osteoblasts requires Tgfbr2 signaling and that decreased bone volume in Osx-Cre;Tgfbr2(fl/fl) mice is likely due to fewer mature osteoblasts. |
