Method: Double-KO mice were created by crossing periostin-and-Sost-KO mice. Phenotypic changes were examined at age of 3-months using combinations of Radiographs, MicroCT, histology, SEM, polarized microscope, and immunohistochemistry and x-gal staining assays.
Result: We first confirmed pathological changes of PDL (disorganized fiber distributions, sharp reduction of biglycan/decorin and pocket formation) and alveolar bone loss in periostin KO mice due to a defect in PDL integrity and inflammation. Unexpectedly, these KO mice displayed a severe osteocyte phenotype (a change of the cell shape from spindle-like to round, a great loss of mineral content surrounding the cell body/dendrites, and reduction of molecular markers such as DMP1). Subsequently, we removed Sost in periostin-KO-osteocytes and showed not only rescues of bone phenotype (osteocyte shape, molecular markers and bone loss) but also improvement of a PDL phenotype, including arrangement and the color of sharpey’s fibers, and expression levels of biglycan/decorin. We also showed close interactions between Sharpey’s fiber and osteocytes. Importantly, we provided direct evidence that osteoblasts/osteocytes in alveolar bone were from PDL progenitor cells using a cell lineage tracing technique in Rosa 26 mice.
Conclusion: Based on a severe osteocyte phenotype observed in periostin-KO mice where removing Sost rescued bone and PDL phenotype, and identification of originations of alveolar bone cells from PDL, we conclude that there is a direct interaction between PDL and alveolar bone via Sharpey’s fibers and osteocytes; and that PDL functions as an important reservoir for alveolar bone modeling and remodeling.