Xu Chunmei, Xie Xudong, Zhao Hu, Wu Yafei, Wang Jun, Feng Jian Q
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Department of Biomedical Sciences, College of Dentistry, Texas A&M University, Dallas, TX, United States.
Front Physiol. 2021 Sep 24;12:721775. doi: 10.3389/fphys.2021.721775. eCollection 2021.
Transforming growth factor beta (TGFβ) 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 TGFβR2 (the key receptor for TGFβ signaling) during postnatal alveolar bone development, we conditionally deleted β in early mesenchymal progenitors by crossing ; β ; mice (named early cKO) or in osteoblasts by crossing β 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 β-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 TGFβ signaling plays critical roles during early alveolar bone formation via the promotion of PDL mesenchymal progenitor proliferation and differentiation mechanisms.
转化生长因子β（TGFβ）信号通路在骨生成过程中发挥着重要作用。然而，该领域的大多数研究都集中在皮质骨和小梁骨，而牙槽骨在很大程度上被忽视了。为了研究TGFβR2（TGFβ信号通路的关键受体）在出生后牙槽骨发育中的作用，我们通过杂交；β；；小鼠（命名为早期cKO）在早期间充质祖细胞中条件性删除β，或通过杂交β小鼠（命名为晚期cKO）在成骨细胞中条件性删除β。两个cKO品系均在出生后第5天（P5）诱导，小鼠在P28处死取材。与对照同窝小鼠相比，早期cKO小鼠的牙槽骨量和骨矿物质密度显著降低，牙周韧带（PDL）出现严重缺陷；相反，晚期cKO小鼠的牙槽骨变化非常小。机制研究表明，PCNA+ PDL细胞数量和OSX+牙槽骨细胞数量显著减少，PDL纤维排列紊乱，骨膜蛋白（最丰富的细胞外基质蛋白）在mRNA和蛋白质水平上均大幅减少。我们还发现早期cKO的PDL中β-连环蛋白大幅减少，而sost（一种有效的Wnt信号抑制剂）大幅增加。基于这些发现，我们得出结论，TGFβ信号通路通过促进PDL间充质祖细胞增殖和分化机制，在早期牙槽骨形成过程中发挥关键作用。
