Intramembranous bone regeneration is a critical process for the success of orthopedic and dental implants. Previous work has shown that periostin plays an important role in intramembranous bone regeneration in the appendicular skeleton. The specific roles of matricellular proteins like Periostin (Postn) and their associated Periostin-expressing cells (PECs) in the calvarial remain largely unexplored. This research investigated the functional requirement of the endogenous Postn gene and de novo PECs during the initial repair phase of a 1.85 mm parietal bone defect in 4-week-old mice.

Utilizing a tamoxifen-inducible Postn-MCM (MerCreMer) genetic system, mice were crossed with either Ai9-tdTomato (tdTM) for lineage tracing or ROSA-DTA (Diphtheria Toxin A) for targeted cell ablation. µCT and immunofluorescence for the differentiating osteoblast marker Osterix were employed one-week post-injury to evaluate structural repair and cellular recruitment.

Results confirmed a highly significant, dose-dependent efficiency in genetic tracing. Volumetric analysis revealed that while Postn deletion did not reach statistical significance, knockout mice exhibited a biologically 2.9-fold increase in the volume of the defect that remained empty compared to haploinsufficient controls. Conversely, functional ablation of PECs via the DTA model did not statistically compromise bone volume or structural repair in either sex. Notably, the recruitment of Osterix-positive cells remained stable across all genotypes, indicating that the osteogenic response is maintained despite Postn deficiency or PECs loss. These findings highlight that, while PECs are indispensable for long bone repair, they appear dispensable for early calvarial regeneration. This suggests that alternative progenitor reservoirs, such as the dura mater or suture-resident PRX1+ stem cells, provide significant regenerative redundancy in the skull. This study establishes a foundational understanding of site-specific skeletal repair.