TGF-Beta Receptor II Is Critical for Osteogenic Progenitor Cell Proliferation and Differentiation During Postnatal Alveolar Bone Formation.
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Transforming growth factor beta (TGF) signaling plays an important role during osteogenesis. However, most research in this area focuses on cortical and trabecular bone, whereas alveolar bone is largely overlooked. To address the role of TGFR2 (the key receptor for TGF signaling) during postnatal alveolar bone development, we conditionally deleted Tgfr2 in early mesenchymal progenitors by crossing Gli1-Cre ERT2; Tgfr2 flox/flox ; R26R tdTomato mice (named early cKO) or in osteoblasts by crossing 3.2kb Col1-Cre ERT2 ; Tgfr2 flox/flox ; R26R tdTomato mice (named late cKO). Both cKO lines were induced at postnatal day 5 (P5) and mice were harvested at P28. Compared to the control littermates, early cKO mice exhibited significant reduction in alveolar bone mass and bone mineral density, with drastic defects in the periodontal ligament (PDL); conversely, the late cKO mice displayed very minor changes in alveolar bone. Mechanism studies showed a significant reduction in PCNA+ PDL cell numbers and OSX+ alveolar bone cell numbers, as well as disorganized PDL fibers with a great reduction in periostin (the most abundant extracellular matrix protein) on both mRNA and protein levels. We also showed a drastic reduction in -catenin in the early cKO PDL and a great increase in SOST (a potent inhibitor of Wnt signaling). Based on these findings, we conclude that TGF signaling plays critical roles during early alveolar bone formation via the promotion of PDL mesenchymal progenitor proliferation and differentiation mechanisms.
