Mitochondrial protein OPA mediates osteoporosis induced by radiation through the P38 signaling pathway
Authors: W-D Wang
X-Q Zhou
G-F Yao
X-J Wang
W-B Kang
Journal: European review for medical and pharmacological sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Bone marrow; mitochondria; OPA; osteoporosis; radiation
Affiliations: Department of Spine and Joint, The 2nd Hospital, Medical College, Shantou University, Shantou University, Shantou, Guangdong, China. .

Abstract:  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. 

Retracted: No

PubPeer comments:
 Please compare Figure 1.  OPA expression in bone marrow cells from osteoporosis mice. A, qRT-PCR detection. B, Western blot detection. C, Western blot analysis *[left]* with *[right]* Figure 1 from [Liu et al (2017)] ,  UCP1 expression in liver cells from mouse liver injury model. (A) qRT-PCR detection. (B) Western blot detection. (C) Western blot analysis . ![file] The two papers appear to be the same part from the replacement of UCP1 with OPA, of  liver injury caused by LPS with  osteoporosis induced by radiation , and  EKR signaling pathway with  P38 signaling pathway . , 
 Above: Figure 2.  P38 signaling is activated, mitochondrial ATP production is reduced, while cell apoptosis is enhanced in bone marrow cells from osteoporosis mice. A, Western blot detection. B, ATP production analysis. C, Cell apoptosis analysis . Below: Figure 2 from Liu et al (2017).  ERK signaling activated, mitochondrial ATP production reduced, and cell apoptosis enhanced in liver injury mouse. (A) Western blot detection. (B) ATP production. (C) Cell apoptosis detection. ![file] Above: Figure 3.  The impact of P38 signaling inhibitor U0126 pretreatment. A, Western blot detection. B, ATP production analysis. C, Cell apoptosis analysis . Below: Figure 3 from Liu et al (2017).  The influence of ERK signaling pathway inhibitor U0126 pretreatment. (A) Western blot detection. (B) ATP production. (C) Cell apoptosis detection . ![file] Above: Figure 4.  OPA and cell apoptosis detection in bone marrow from osteoporosis patients. A, Western blot detection. B, ATP production analysis. C, Cell apoptosis analysis . Below: Figure 4.  UCP1 expression and cell apoptosis in the liver tissue from sepsis patients. (A) Western blot detection. (B) ATP production. (C) Cell apoptosis detection. ![file] ,