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.
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*

Objective:To evaluate the effect of five external treatment methods of traditional Chinese medicine on the pain of patients with lumbar disc herniation (LDH) through a network Meta-analysis.Methods:The published article on the effect of external treatment methods of Traditional Chinese Medicine in patients with LDH was retrieved by computer in China National Knowledge Infrastructure, WanFang Database, VIP, China Biomedical Database, PubMed, Cochrane Library and Web of Science. The retrieval time limit was from the establishment of the database to May 31, 2022. Two researchers independently screened the article according to the inclusion and exclusion criteria, extracted the information and evaluated the quality. Review Manger 5.4 software was used to draw the bias risk map and Stata SE 16.0 software was used to conduct the network Meta-analysis.Results:A total of 1 133 patients were included in 12 articles, and there were five kinds of external treatment methods of Traditional Chinese Medicine. The results of network Meta-analysis showed that except for acupoint application, scraping, Traditional Chinese Medicine iontophoresis, Traditional Chinese Medicine scalding, auricular point sticking had statistically significant differences in the effect of pain compared with conventional treatment and nursing ( P<0.05). There were no statistically significant differences between the five external treatment methods of Traditional Chinese Medicine ( P>0.05). The cumulative ranking plot showed that scraping was the best intervention method for pain in LDH patients, with a surface under the cumulative ranking ( SUCRA) value of 80.3%. Conclusions:Scraping is the best external treatment of traditional Chinese medicine to relieve the pain of LDH patients, but it still needs to be further demonstrated by a large number of high-quality randomized controlled trials.