Progranulin Promotes Regeneration of Inflammatory Periodontal Bone Defect in Rats via Anti-inflammation, Osteoclastogeni
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ORIGINAL ARTICLE
Progranulin Promotes Regeneration of Inflammatory Periodontal Bone Defect in Rats via Anti-inflammation, Osteoclastogenic Inhibition, and Osteogenic Promotion Qian Chen,1,2 Jun Cai,3 Xiao Li,4 Aimei Song,2 Hongmei Guo,2 Qinfeng Sun,2 Chengzhe Yang,5,7 and Pishan Yang 1,2,6,7
Abstract— Progranulin (PGRN) has been proved to play a crucial role in antiinflammation 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. KEY WORDS: Anti-inflammatory agents; Growth factors; Experimental periodontitis; Periodontal regeneration; Tumor necrosis factor-α.
1
Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Shandong University, Jinan, Shandong, China 2 Department of Periodontology, School of Dentistry, Shandong University, Jinan, Shandong, China 3 Department of Comprehensive Dentistry, Jinan Stomatological Hospital, Jinan, Shandong, China 4 Department of Periodontology, Jinan Stomatological Hospital, Jinan, Shandong, China 5 Department of Oral and Maxillofacial Surgery, Qilu Hospital, and Institute of Stomatology, Shandong University, Jinan, Shandong, China
6
Department of Periodontology, School of Stomatology, Shandong University, Jinan, Shandong, China 7 To whom correspondence should be addressed to Chengzhe Yang at Department of Oral and Maxillofacial Surgery, Qilu Hospital, and Institute of Stomatology, Shandong University, Jinan, Shandong, China. E-mail: [email protected]; and Pishan Yang at Department of Perio
