Progranulin Promotes Regeneration of Inflammatory Periodontal Bone Defect in Rats via Anti-inflammation, Osteoclastogenic Inhibition, and Osteogenic Promotion

Progranulin (PGRN) has been proved to play a crucial role in anti-inflammation and osteogenesis promotion; thus, it was hypothesized that PGRN could promote bone regeneration in periodontal disease. In this experiment, the periodontal bone defects were established in periodontitis rats; recombinant human progranulin (rhPGRN), tumor necrosis factor alpha inhibitor (anti-TNF-α), or phosphate buffer saline (PBS)-loaded collagen membrane scaffolds were implanted within defects and the rats were sacrificed at scheduled time points. Volume of new bone was assessed by radiological and histomorphometric analyses. Expression of osteogenesis-related markers and tumor necrosis factor-α (TNF-α) was evaluated using immunohistochemistry. Tartrate-resistant acid phosphatase (TRAP) staining was also performed to determine the number of osteoclasts. Immunofluorescence (IF) staining was performed to explore the interaction between rhPGRN and tumor necrosis factor receptors (TNFRs). The results showed that the rhPGRN group had significantly superior quantity and quality of newly formed bone, higher expression of alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2), and TNFR2 compared with the PBS group and the anti-TNF-α group. Similarly to the anti-TNF-α group, the rhPGRN group also exhibited the significant inhibitory effect on the expression of TNF-α and the number of TRAP-positive cells compared with the PBS group. Hence, our experiment suggests that PGRN promotes regeneration of inflammatory periodontal bone defect in rats via anti-inflammation, osteoclastogenic inhibition, and osteogenic promotion. Local administration of PGRN may provide a new therapeutic strategy for periodontal bone regeneration.