State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Med-X Center for Materials, Department of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Department of Biomedical Sciences, Texas A&M University College of Dentistry, Dallas, Texas, USA.
J Clin Periodontol. 2022 Sep;49(9):945-956. doi: 10.1111/jcpe.13666. Epub 2022 Jul 8.
To date, controversies still exist regarding the exact cellular origin and regulatory mechanisms of periodontium development, which hinders efforts to achieve ideal periodontal tissue regeneration. Axin2-expressing cells in the periodontal ligament (PDL) have been shown to be a novel progenitor cell population that is essential for periodontal homeostasis. In the current study, we aimed to elucidate the regulatory role of bone morphogenetic protein receptor type 1A (BMPR1A)-mediated BMP signalling in Axin2-expressing cells during periodontium development.
Two strains of Axin2 gene reporter mice, Axin2 and Axin2 ; R26R mice, were used. We next generated Axin2 ; R26R ; R26R mice to genetically ablate of Axin2-lineage cells. Axin2 ; Bmpr1a ; R26R mice were established to conditionally knock out Bmpr1a in Axin2-lineage cells. Multiple approaches, including micro-computed tomography, calcein green, and alizarin red double-labelling, scanning electron microscopy, and histological and immunostaining assays, were used to analyse periodontal phenotypes and molecular mechanisms.
X-gal staining revealed that Axin2-expressing cells in the PDL were mainly distributed along the alveolar bone and cementum surface. Cell lineage tracing and cell ablation assays further demonstrated the indispensable role of Axin2-expressing cells in periodontium development. Next, we found that conditional knockout of Bmpr1a in Axin2-lineage cells led to periodontal defects, which were characterized by alveolar bone loss, impaired cementogenesis, and abnormal Sharpey's fibres.
Our findings suggest that Axin2-expressing cells in the PDL are essential for periodontium development, which is regulated by BMP signalling.
迄今为止，牙周组织发育的确切细胞起源和调控机制仍存在争议，这阻碍了实现理想牙周组织再生的努力。牙周韧带（PDL）中表达 Axin2 的细胞已被证明是一种新型祖细胞群体，对于牙周稳态至关重要。在本研究中，我们旨在阐明骨形态发生蛋白受体 1A（BMPR1A）介导的 BMP 信号在牙周组织发育过程中对 Axin2 表达细胞的调控作用。
使用了两种 Axin2 基因报告小鼠，Axin2 和 Axin2 ; R26R 小鼠。接下来，我们生成了 Axin2 ; R26R ; R26R 小鼠以遗传消融 Axin2 谱系细胞。建立了 Axin2 ; Bmpr1a ; R26R 小鼠以条件性敲除 Axin2 谱系细胞中的 Bmpr1a。我们采用了多种方法，包括微计算机断层扫描、钙黄绿素绿和茜素红双重标记、扫描电子显微镜以及组织学和免疫染色分析，来分析牙周表型和分子机制。
X-gal 染色显示，PDL 中的 Axin2 表达细胞主要分布在牙槽骨和牙骨质表面。细胞谱系追踪和细胞消融实验进一步证明了 Axin2 表达细胞在牙周组织发育中的不可或缺作用。接下来，我们发现条件性敲除 Axin2 谱系细胞中的 Bmpr1a 导致牙周缺陷，其特征为牙槽骨丧失、牙骨质形成受损和异常的 Sharpey 纤维。
我们的研究结果表明，PDL 中的 Axin2 表达细胞对于牙周组织发育至关重要，其受 BMP 信号的调控。
