State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
Biomolecules. 2024 Oct 17;14(10):1318. doi: 10.3390/biom14101318.
Bone is a dynamic organ with an active metabolism and high sensitivity to mitochondrial dysfunction. The mitochondrial permeability transition pore (mPTP) is a low-selectivity channel situated in the inner mitochondrial membrane (IMM), permitting the exchange of molecules of up to 1.5 kDa in and out of the IMM. Recent studies have highlighted the critical role of the mPTP in bone tissue, but there is currently a lack of reviews concerning this topic. This review discusses the structure and function of the mPTP and its impact on bone-related cells and bone-related pathological states. The mPTP activity is reduced during the osteogenic differentiation of mesenchymal stem cells (MSCs), while its desensitisation may underlie the mechanism of enhanced resistance to apoptosis in neoplastic osteoblastic cells. mPTP over-opening triggers mitochondrial swelling, regulated cell death, and inflammatory response. In particular, mPTP over-opening is involved in dexamethasone-induced osteoblast dysfunction and bisphosphonate-induced osteoclast apoptosis. In vivo, the mPTP plays a significant role in maintaining bone homeostasis, with many bone disorders linked to its excessive opening. Genetic deletion or pharmacological inhibition of the over-opening of mPTP has shown potential in enhancing bone injury recovery and alleviating bone diseases. Here, we review the findings on the relationship of the mPTP and bone at both the cellular and disease levels, highlighting novel avenues for pharmacological approaches targeting mitochondrial function to promote bone healing and manage bone-related disorders.
骨骼是一种具有活跃新陈代谢和对线粒体功能障碍高度敏感的动态器官。线粒体通透性转换孔（mPTP）是位于线粒体内膜（IMM）中的一种低选择性通道，允许分子量高达 1.5 kDa 的分子在 IMM 内外交换。最近的研究强调了 mPTP 在骨组织中的关键作用，但目前缺乏关于该主题的综述。本综述讨论了 mPTP 的结构和功能及其对与骨相关的细胞和与骨相关的病理状态的影响。mPTP 活性在间充质干细胞（MSCs）的成骨分化过程中降低，而其脱敏可能是肿瘤成骨细胞对细胞凋亡增强的机制。mPTP 过度开放会引发线粒体肿胀、调节性细胞死亡和炎症反应。特别是，mPTP 过度开放参与了地塞米松诱导的成骨细胞功能障碍和双膦酸盐诱导的破骨细胞凋亡。在体内，mPTP 在维持骨稳态中起着重要作用，许多骨疾病都与其过度开放有关。mPTP 的基因缺失或药理学抑制已显示出在促进骨损伤恢复和缓解骨疾病方面的潜力。在这里，我们综述了 mPTP 与细胞和疾病水平的骨之间的关系的研究结果，强调了靶向线粒体功能的药理学方法在促进骨愈合和管理与骨相关的疾病方面的新途径。
