Hard Tissue Biointerface Research Center, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea; Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea.
Department of Biotechnology, School of Engineering, Daegu University, Gyeongsan, Republic of Korea.
Biochem Biophys Res Commun. 2019 Dec 3;520(2):459-465. doi: 10.1016/j.bbrc.2019.10.048. Epub 2019 Oct 10.
The peroxisome proliferator-activated receptor (PPAR)-α agonist fenofibrate is used as a lipid-lowering agent to reduce cholesterol and triglyceride in blood. In this study, we investigated whether fenofibrate affects osteoblast differentiation of osteogenic precursor cells. Quantitative real-time PCR and alkaline phosphatase (ALP) staining assays revealed that fenofibrate can enhance the osteoblast differentiation of C3H10T1/2 and MC3T3-E1 cells. In contrast with fenofibrate, the PPARγ agonist rosiglitazone decreased or did not affect the expression of osteogenic genes in these cells. Fenofibrate dose- and time-dependently increased PPARα expression, and concomitantly increased the expression of bone morphogenetic protein 2 (BMP2). Knockdown of PPARα abolished fenofibrate-induced BMP2 expression, activity of the BMP2 promoter gene, and calcium deposition. The chromatin immunoprecipitation assay demonstrated that fenofibrate increased BMP2 expression by inducing direct binding of PPARα to the BMP2 promoter region. Taken together, we suggest that fenofibrate has a stimulatory effect on osteoblast differentiation via the elevation of PPARα levels and the PPARα-mediated BMP2 expression. Our findings provide fenofibrate as a useful agent for controlling hypercholesterolemic patients with osteoporosis.
过氧化物酶体增殖物激活受体 (PPAR)-α 激动剂非诺贝特被用作降脂药，以降低血液中的胆固醇和甘油三酯。在这项研究中，我们研究了非诺贝特是否会影响成骨前体细胞的成骨细胞分化。实时定量 PCR 和碱性磷酸酶 (ALP) 染色检测表明，非诺贝特可以增强 C3H10T1/2 和 MC3T3-E1 细胞的成骨细胞分化。与非诺贝特相反，PPARγ 激动剂罗格列酮降低或不影响这些细胞中成骨基因的表达。非诺贝特呈剂量和时间依赖性地增加了 PPARα 的表达，并同时增加了骨形态发生蛋白 2 (BMP2) 的表达。PPARα 的敲低消除了非诺贝特诱导的 BMP2 表达、BMP2 启动子基因的活性和钙沉积。染色质免疫沉淀分析表明，非诺贝特通过诱导 PPARα 与 BMP2 启动子区域的直接结合，增加了 BMP2 的表达。总之，我们认为非诺贝特通过升高 PPARα 水平和 PPARα 介导的 BMP2 表达对成骨细胞分化具有刺激作用。我们的研究结果表明，非诺贝特是控制高胆固醇血症骨质疏松症患者的有用药物。
