Details

Autor(en) / Beteiligte

• Peters, Sarah B.
• Wang, Ying
• Serra, Rosa

Titel

Tgfbr2 is required in osterix expressing cells for postnatal skeletal development

Ist Teil von

• Bone (New York, N.Y.), 2017-04, Vol.97, p.54-64

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• Transforming growth factor β (TGFβ) is known to play an important role in early skeletal development. We previously demonstrated that loss of TGFβ receptor II (Tgfbr2) in Prx1-Cre-expressing mesenchyme results in defects in long bones, joints, and the skull vault in mice resulting from reduced naïve 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;Tgfbr2fl/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;Tgfbr2fl/fl mice is likely due to fewer mature osteoblasts. •Tgfbr2 is required in Osx-Cre expressing osteoblasts for postnatal development of trabecular, cortical, and calvaria bones.•Limb length and the length of the prehypertrophic zones of the growth plate were reduced in Tgfbr2-deleted mice.•Deletion of Tgfbr2 in immature osteoblasts resulted in reduced osteoblast proliferation and number in postnatal bone.•There was a reduction in Bglap, a marker for mature osteoblasts, in Tgfbr2 deleted bone.•Low bone volume in Tgfbr2 deleted mice is due to decreased osteoblast proliferation resulting in fewer mature osteoblasts.