Wang Ruyi, Li Yuan, Tan Bowen, Li Shijia, Wu Yanting, Chen Yao, Qian Yuran, Wang Haochen, Li Bo, Zhao Zhihe, Yuan Quan, Li Yu
State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Int J Oral Sci. 2025 Sep 2;17(1):63. doi: 10.1038/s41368-025-00392-6.
Insufficient alveolar bone thickness increases the risk of periodontal dehiscence and fenestration, especially in orthodontic tooth movement. Abaloparatide (ABL), a synthetic analog of human PTHrP (1-34) and a clinical medication for treating osteoporosis, has recently demonstrated its potential in enhancing craniofacial bone formation. Herein, we show that intraoral submucosal injection of ABL, when combined with mechanical force, promotes in situ alveolar bone thickening. The newly formed bone is primarily located outside the original compact bone, implying its origin from the periosteum. RNA sequencing of the alveolar bone tissue revealed that the focal adhesion (FA) pathway potentially mediates this bioprocess. Local injection of ABL alone enhances cell proliferation, collagen synthesis, and phosphorylation of focal adhesion kinase (FAK) in the alveolar periosteum; when ABL is combined with mechanical force, the FAK expression is upregulated, in line with the accomplishment of the ossification. In vitro, ABL enhances proliferation, migration, and FAK phosphorylation in periosteal stem cells. Furthermore, the pro-osteogenic effects of ABL on alveolar bone are entirely blocked when FAK activity is inhibited by a specific inhibitor. In summary, abaloparatide combined with mechanical force promotes alveolar bone formation via FAK-mediated periosteal osteogenesis. Thus, we have introduced a promising therapeutic approach for drug-induced in situ alveolar bone augmentation, which may prevent or repair the detrimental periodontal dehiscence, holding significant potential in dentistry.
牙槽骨厚度不足会增加牙周裂和开窗的风险，尤其是在正畸牙齿移动过程中。阿巴洛肽（ABL）是一种人甲状旁腺激素相关蛋白（1-34）的合成类似物，也是一种治疗骨质疏松症的临床药物，最近已显示出其在促进颅面骨形成方面的潜力。在此，我们表明，将ABL经口内粘膜下注射并结合机械力，可促进原位牙槽骨增厚。新形成的骨主要位于原始密质骨之外，这意味着其起源于骨膜。牙槽骨组织的RNA测序显示，粘着斑（FA）通路可能介导了这一生物学过程。单独局部注射ABL可增强牙槽骨膜中的细胞增殖、胶原合成以及粘着斑激酶（FAK）的磷酸化；当ABL与机械力结合时，FAK表达上调，这与骨化的完成相一致。在体外，ABL可增强骨膜干细胞的增殖、迁移以及FAK磷酸化。此外，当FAK活性被特异性抑制剂抑制时，ABL对牙槽骨的促骨生成作用完全被阻断。总之，阿巴洛肽与机械力相结合可通过FAK介导的骨膜成骨促进牙槽骨形成。因此，我们引入了一种有前景的治疗方法用于药物诱导的原位牙槽骨增量，这可能预防或修复有害的牙周裂，在牙科领域具有巨大潜力。
