Local abaloparatide administration promotes in situ alveolar bone augmentation via FAK-mediated periosteal osteogenesis.
10.1038/s41368-025-00392-6
- Author:
Ruyi WANG
1
;
Yuan LI
1
;
Bowen TAN
1
;
Shijia LI
1
;
Yanting WU
1
;
Yao CHEN
1
;
Yuran QIAN
1
;
Haochen WANG
1
;
Bo LI
1
;
Zhihe ZHAO
1
;
Quan YUAN
2
;
Yu LI
3
Author Information
1. 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.
2. 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. yuanquan@scu.edu.cn.
3. 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. yuli@scu.edu.cn.
- Publication Type:Journal Article
- MeSH:
Osteogenesis/drug effects*;
Periosteum/cytology*;
Parathyroid Hormone-Related Protein/administration & dosage*;
Animals;
Focal Adhesion Protein-Tyrosine Kinases/metabolism*;
Alveolar Process/drug effects*;
Cell Proliferation/drug effects*;
Phosphorylation;
Rats;
Male;
Humans;
Focal Adhesion Kinase 1/metabolism*;
Cell Movement/drug effects*
- From:
International Journal of Oral Science
2025;17(1):63-63
- CountryChina
- Language:English
-
Abstract:
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.
