Peroxisome proliferator activated receptor γ promotes mineralization and differentiation in cementoblasts via inhibiting Wnt/β-catenin signaling pathway
Peroxisome proliferator activated receptor γ promotes mineralization and differentiation in cementoblasts via inhibiting Wnt/β-catenin signaling pathway
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过氧化物酶体增殖物激活受体γ通过抑制Wnt/β-连环蛋白信号通路促进成牙骨质细胞矿化和分化
DOI：
10.1002/jcb.29509
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发表时间：
2019-11-11
影响因子：
4
通讯作者：
Song, Yaling
中科院分区：
文献类型：
--
作者：
Hu, Yingying;Wang, Changning;Song, Yaling
过氧化物酶体增殖物激活受体γ (PPAR γ)是核受体转录因子家族的一员，参与炎症调节和骨重塑。很少有研究探讨PPAR γ对成水泥细胞矿化和分化的影响。为了探索修复牙周组织特别是牙骨质损伤的潜在途径，本研究旨在探讨PPAR γ对牙骨质母细胞矿化和分化的影响及其调控机制。小鼠成水泥细胞系OCCM-30分别加入二甲亚氧化物、罗格列酮（PPAR γ激动剂）、GW9662 （PPAR γ拮抗剂）、氯化锂（LiCl）、肿瘤坏死因子- α (tnf - α)或各自的组合，在碱性培养基中培养24小时/48小时或在矿化培养基中培养3/7/10天。采用实时定量聚合酶链反应和Western blot检测矿化基因碱性磷酸酶（ALP）、矮子相关转录因子2 （RUNX2）和骨钙素（OCN）的表达。用ALP染色和茜素红染色评价OCCM-30细胞的矿化程度。Western blot和免疫荧光分析β -catenin在细胞质/细胞核内表达和易位的变化。结果显示，PPAR γ激动剂罗格列酮提高了ALP、RUNX2和OCN的表达，加深了ALP染色，增加了矿化结节的形成，降低了细胞核中β -catenin的表达。LiCl是Wnt信号通路的激活剂，可以抑制矿化基因的表达，逆转罗格列酮导致的矿化基因表达上调。在炎症微环境下，罗格列酮不仅可以抑制tnf - α引起的白细胞介素-1 β的表达，还可以提高OCCM-30细胞矿化基因的表达。综上所述，PPAR γ可以通过抑制Wnt/ β -catenin信号通路促进成牙骨质细胞矿化和分化，这将为牙周炎的治疗和牙周组织再生提供新的思路。
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.