Peroxisome proliferator activated receptor γ promotes mineralization and differentiation in cementoblasts via inhibiting Wnt/β-catenin signaling pathway

Peroxisome proliferator activated receptor gamma (PPAR gamma) is a member of the nuclear receptor family of transcription factors, which involved in inflammation regulating and bone remodeling. Rare studies explored the effects of PPAR gamma on mineralization and differentiation in cementoblasts. To explore the potential approaches to repair the damaged periodontal tissues especially for cementum, the present study aims to investigate the effects and the regulating mechanism of PPAR gamma on mineralization and differentiation in cementoblasts. Murine cementoblast cell lines (OCCM-30) were cultured in basic medium for 24 hours/48 hours or in mineralization medium for 3/7/10 days, respectively at addition of dimethyl sulphoxide, rosiglitazone (PPAR gamma agonist), GW9662 (PPAR gamma antagonist), lithium chloride (LiCl), tumor necrosis factor-alpha (TNF-alpha), or respective combination. Expression of mineralization genes alkaline phosphatase (ALP), runt related transcription factors 2 (RUNX2), and osteocalcin (OCN) were detected by quantitative real-time polymerase chain reaction or/and Western blot. ALP staining and alizarin red staining were used to evaluate the mineralization in OCCM-30 cells. The change of beta-catenin expression and translocation in cytoplasm/nucleus was analyzed by Western blot and immunofluorescence. The results showed that PPAR gamma agonist rosiglitazone improved the expression of ALP, RUNX2, and OCN, deepened ALP staining, increased mineralized nodules formation, and decreased beta-catenin expression in the nucleus. LiCl, an activator of the Wnt signaling pathway, inhibited the expression of mineralization genes and reversed the upregulated expression of mineralization genes resulted from rosiglitazone. Under inflammatory microenvironment, rosiglitazone not only suppressed the expression of interleukin-1 beta caused by TNF-alpha, but improved the expression of mineralization genes in OCCM-30 cells. In conclusion, PPAR gamma could promote mineralization and differentiation in cementoblasts via inhibiting the Wnt/beta-catenin signaling pathway, which would shed new light on the treatment of periodontitis and periodontal tissue regeneration.