PTHrP Overexpression in Periosteum Promotes Alveolar Bone Formation

作者：Yu Chen, B. Zhang, Bo Li, Y. Wu, J. Zhong, Y. Li, Y. Li, R. Wang, W. Guo, Y. Fan, Y. Li, Y. Li · 发表于：Journal of Dental Research · 年份：2026 · DOI：10.1177/00220345261443475 · 被引用次数：1 · 研究领域：Bone health and treatments、Oral health in cancer treatment、Bone Tissue Engineering Materials

Alveolar bone regions with low innate thickness are prone to dehiscence, potentially causing harmful gingival recession. In situ alveolar bone thickening via local bioagent administration has recently emerged as a promising research area. Parathyroid hormone-related protein (PTHrP), encoded by the Pthlh gene, plays a pivotal role in skeletal development and bone remodeling. In this study, we developed a recombinant adeno-associated virus (rAAV) vector overexpressing Pthlh (rAAV9- Pthlh ). Using a split-mouth design, we administered rAAV9- Pthlh via a single submucosal injection into the right maxillary buccal gingiva of rats. Micro-computed tomography scans, both in vivo and ex vivo, revealed a significant increase in alveolar bone thickness on the PTHLH sides 6 wk post-transfection. This enhanced alveolar bone formation was accompanied by marked periosteal thickening, with elevated expression of PTHrP, parathyroid hormone 1 receptor (PTH1R), OCN, and COL1A1. RNA sequencing of the buccal bone tissue showed upregulation of osteogenesis-related pathways along with increased mitophagy activity. Immunofluorescence confirmed enhanced colocalization of mitochondrial and lysosomal markers in the PTHLH group, primarily in the periosteum. Overexpressing Pthlh in primary rat periosteal stem cells via lentiviral transduction promoted cell proliferation and migration and elevated expression of COL1A1, as well as mitophagy markers BNIP3 and LC3-II. These effects were mitigated by Mdivi-1,...