PGC-1 alpha regulates mitochondrial biogenesis to ameliorate hypoxia-inhibited cementoblast mineralization
PGC-1 alpha regulates mitochondrial biogenesis to ameliorate hypoxia-inhibited cementoblast mineralization
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PGC-1 α 调节线粒体生物发生以改善缺氧抑制的成牙骨质细胞矿化
DOI：
10.1111/nyas.14872
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发表时间：
2022-08-02
影响因子：
5.2
通讯作者：
Cao，Zhengguo
中科院分区：
文献类型：
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作者：
Wang，Huiyi;Wang，Xiaoxuan;Cao，Zhengguo
缺氧通常发生在炎症组织中，例如受牙周炎和根尖牙周炎病变影响的组织。线粒体的生物合成在缺氧时会被破坏。过氧化物酶体增殖物激活受体γ辅激活因子-1 α（PGC-1α）是线粒体生物发生所需的核心因子。成牙骨质细胞是牙根表面的衬里细胞，在牙骨质形成中起着不可或缺的作用。缺氧对成牙骨质细胞的影响及其机制，特别是缺氧过程中线粒体生物合成的研究还很缺乏。在本研究中，我们发现缺氧诱导因子-1 α在活体根尖周炎组织中表达升高。相反，根尖周病变表现出PGC-1α表达的减少。在体外实验中，使用氯化钴（CoCl 2）诱导缺氧。我们观察到CoCl 2诱导的缺氧抑制成牙骨质细胞的矿化能力和线粒体生物合成，伴随着异常的线粒体形态。此外，我们发现CoCl 2阻断p38通路，同时激活Erk 1/2通路，前者上调PGC-1α的表达，而后者逆转了这一效应。总体而言，我们的研究结果表明，在CoCl 2诱导的缺氧背景下，牙骨质形成过程中线粒体生物合成（尤其是通过PGC-1α）受损，这取决于丝裂原活化蛋白激酶信号通路。
Hypoxia often occurs in inflammatory tissues, such as tissues affected by periodontitis and apical periodontitis lesions. Mitochondrial biogenesis can be disrupted in hypoxia. Peroxisome proliferator‐activated receptor gamma coactivator‐1 alpha (PGC‐1α) is a core factor required for mitochondrial biogenesis. Cementoblasts are root surface lining cells that play an integral role in cementum formation. There is a dearth of research on the effect of hypoxia on cementoblasts and underlying mechanisms, particularly in relation to mitochondrial biogenesis during the hypoxic process. In this study, we found that the expression of hypoxia inducible factor‐1α was elevated in apical periodontitis tissuesin vivo. In contrast, periapical lesions exhibited a reduction of PGC‐1α expression. Forin vitroexperiments, cobalt chloride (CoCl2) was used to induce hypoxia. We observed that CoCl2‐induced hypoxia suppressed the mineralization ability and mitochondrial biogenesis of cementoblasts, accompanied by abnormal mitochondria morphology. Furthermore, we found that CoCl2blocked the p38 pathway, while it activated the Erk1/2 pathway, with the former upregulating the expression of PGC‐1α, while the latter reversed the effects. Overall, our findings demonstrate that mitochondrial biogenesis, especially via PGC‐1α, is impaired during cementogenesis in the context of CoCl2‐induced hypoxia, dependent on the mitogen‐activated protein kinase signaling pathway.