PPARδ-mediated mitochondrial rewiring of osteoblasts determines bone mass
PPARδ-mediated mitochondrial rewiring of osteoblasts determines bone mass
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DOI：
10.1038/s41598-020-65305-5
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发表时间：
2020-05-21
影响因子：
4.6
通讯作者：
Kroenke, Gerhard
中科院分区：
文献类型：
--
作者：
Mueller, Dorothea I. H.;Stoll, Cornelia;Kroenke, Gerhard
骨转换是由破骨细胞介导的骨吸收和成骨细胞介导的骨形成决定的，是一个高能量消耗的过程。然而，成骨细胞分化和矿化对正常骨形成的代谢需求仍不完全清楚。在这里，我们发现核受体过氧化物酶体增殖激活受体(PPAR) δ是成骨细胞代谢的关键调节因子。PPAR δ的诱导对于成骨细胞的分化和矿化所必需的代谢适应和线粒体呼吸速率的增加是必不可少的。反过来，小鼠中PPAR δ的成骨细胞特异性缺失导致成骨细胞能量稳态改变，矿化受损和骨量减少。这些数据表明，PPAR δ是成骨细胞代谢的关键调节因子，并强调了成骨细胞介导的骨形成和骨转换过程中细胞代谢重新布线的相关性。
Bone turnover, which is determined by osteoclast-mediated bone resorption and osteoblast-mediated bone formation, represents a highly energy consuming process. The metabolic requirements of osteoblast differentiation and mineralization, both essential for regular bone formation, however, remain incompletely understood. Here we identify the nuclear receptor peroxisome proliferator-activated receptor (PPAR) delta as key regulator of osteoblast metabolism. Induction of PPAR delta was essential for the metabolic adaption and increased rate in mitochondrial respiration necessary for the differentiation and mineralization of osteoblasts. Osteoblast-specific deletion of PPAR delta in mice, in turn, resulted in an altered energy homeostasis of osteoblasts, impaired mineralization and reduced bone mass. These data show that PPAR delta acts as key regulator of osteoblast metabolism and highlight the relevance of cellular metabolic rewiring during osteoblast-mediated bone formation and bone-turnover.