Department of Spine and Joint, The 2nd Hospital, Medical College, Shantou University, Shantou University, Shantou, Guangdong, China.
Eur Rev Med Pharmacol Sci. 2018 Dec;22(23):8091-8097. doi: 10.26355/eurrev_201812_16499.
Bone marrow is full of mitochondria. However, the role of bone marrow mitochondrial protein in bone marrow damage and related signal transduction mechanism remains to be further studied. OPA is a newly discovered mitochondrial transmembrane protein. Its expression pattern and function in the physiological and pathological conditions of bone marrow are still elusive. The purpose of this study is to investigate the potential role of OPA in osteoporosis.
A mouse osteoporosis model was established by radiation. The OPA expression was tested by Western blot and qRT-PCR. The P38 signaling activity was evaluated by enzymatic activity kit. The mitochondrial ATP production was determined by flow cytometry. The bone marrow cell apoptosis was detected by flow cytometry. U0126 was used to pretreat mouse before modeling. Bone marrow tissue was collected from patients who received osteoporosis surgery to test the OPA expression, P38 activation and cell apoptosis. The OPA and P38 levels were analyzed by correlation.
The mouse osteoporosis model was successfully established by radiation induction. In this osteoporosis model, the expression of OPA was increased. The P38 signaling was activated while the mitochondrial ATP production was reduced, with the increase of apoptosis of bone marrow cells. By contrast, U0126 pretreatment markedly inhibited the OPA expression, restrained the P38 signaling pathway, enhanced mitochondrial ATP production and suppressed the bone marrow cell apoptosis in mouse osteoporosis model. A significantly positive correlation was found between OPA and P38.
The down-regulation of OPA inhibits cell apoptosis and improves osteoporosis via inducing mitochondrial ATP production and suppressing the P38 signaling pathway.
骨髓中充满了线粒体。然而，骨髓线粒体蛋白在骨髓损伤及相关信号转导机制中的作用仍有待进一步研究。OPA 是一种新发现的线粒体跨膜蛋白。其在骨髓生理和病理条件下的表达模式和功能仍不清楚。本研究旨在探讨 OPA 在骨质疏松症中的潜在作用。
采用放射法建立小鼠骨质疏松症模型。通过 Western blot 和 qRT-PCR 检测 OPA 表达。通过酶活性试剂盒评估 P38 信号活性。通过流式细胞术测定线粒体 ATP 产生。通过流式细胞术检测骨髓细胞凋亡。在建模前用 U0126 预处理小鼠。收集接受骨质疏松症手术患者的骨髓组织，检测 OPA 表达、P38 激活和细胞凋亡。通过相关性分析 OPA 和 P38 水平。
通过放射诱导成功建立了小鼠骨质疏松症模型。在该骨质疏松症模型中，OPA 的表达增加。P38 信号被激活，而线粒体 ATP 产生减少，同时骨髓细胞凋亡增加。相比之下，U0126 预处理显著抑制了 OPA 的表达，抑制了 P38 信号通路，增强了线粒体 ATP 的产生，并抑制了小鼠骨质疏松症模型中的骨髓细胞凋亡。OPA 和 P38 之间存在显著的正相关。
下调 OPA 通过诱导线粒体 ATP 产生和抑制 P38 信号通路抑制细胞凋亡，改善骨质疏松症。
