title: Tgfbr2 is required in osterix expressing cells for postnatal skeletal development.
abstract: 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/flmice 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/flmice is likely due to fewer mature osteoblasts.
authors.affiliation: Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, 1918 University Boulevard, Birmingham AL 35294, USA.
authors.forename: Sarah B
authors.initials: SB
authors.lastname: Peters
authors.affiliation: Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, 1918 University Boulevard, Birmingham AL 35294, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, 1918 University Boulevard, Birmingham AL 35294, USA. Electronic address: rserra@uab.edu.
authors.forename: Rosa
authors.initials: R
authors.lastname: Serra
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count; D002454:Cell Differentiation; D049109:Cell Proliferation; D005269:Femur / Q000000981:diagnostic imaging; D017353:Gene Deletion; D055785:Gene Knockdown Techniques; D006132:Growth Plate / Q000166:cytology / Q000378:metabolism; D019426:Integrases / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009929:Organ Size; D010006:Osteoblasts / Q000166:cytology; D010012:Osteogenesis; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D012886:Skull / Q000166:cytology; D000076182:Sp7 Transcription Factor / Q000378:metabolism*; D055114:X-Ray Microtomography
chemical_list: D018125:Receptors, Transforming Growth Factor beta; D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; C045073:Cre recombinase; D019426:Integrases
keywords: Calvaria; Long bone; Osteoblast differentiation; Osteogenesis; Proliferation; Tgfbr2