Mitochondrial protein OPA mediates osteoporosis induced by radiation through the P38 signaling pathway

W.-D. Wang, W.-B. Kang, X.-Q. Zhou, G.-F. Yao, X.-J. Wang

Department of Spine and Joint, The 2nd Hospital, Medical College, Shantou University, Shantou University, Shantou, Guangdong, China. oucmxyy76kcn14@sina.com

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• Orthopedics

OBJECTIVE: 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.

PATIENTS AND METHODS: 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.

RESULTS: 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.

CONCLUSIONS: The down-regulation of OPA inhibits cell apoptosis and improves osteoporosis via inducing mitochondrial ATP production and suppressing the P38 signaling pathway.

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