Résumé
Objective To investigate the protective effect of menatetrenone (MK4) on the osteoblasts in oxidative stress, and to clarify the anti-osteoporosis mechanism of MK4. Methods Mouse osteoblasts (MC3T3-E1) induced by hydrogen peroxide (H2O2) was used. Cell viability, ALP activity and the area of bone nodule were observed. The level of ROS was detected by DCFH-DA, mitochondrial membrane potential by JC-1, apoptosis rate by annexin V-FITC/PI, and the expression of FoxO1, FoxO3, SOD, bcl-2 and bax by RT-PCR. Results Menatetrenone at 10 μmol/L significantly increased the proliferation of osteoblasts stimulated by H2O2, ALP activity, bone nodule formation area, cell membrane potential, the antioxidant SOD and transcription factors FoxO1 and FoxO3 mRNA expression. In the meantime, the elevated malondialdehyde and reactive oxygen species level in cells induced by H2O2, the apoptosis rate and the mRNA expression level of bax/Bcl-2 were significantly reduced. Conclusion menatetrenone can protect osteoblasts from oxidative damage by regulating FoxO pathway and reduce osteoblasts apoptosis by up regulating the proportion of Bcl-2/bax.
Résumé
BACKGROUND: Posttransplant osteoporosis in renal transplant recipient is frequently observed complications, but therapeutic modalities are not clearly elucidated. Recent studies indicate that vitamin K2 also play a role in bone metabolism. Therefore, we performed prospective study to evaluate the effect of vitamin K2 (Menatetrenone(R)) on posttransplant osteroporosis. METHODS: Our study included total 83 patients (40 male, 43 female; age 36.9+/-5.5 years) who received a renal transplant more than 6 months ago. They underwent dual-energy X-ray absorptiometry (DEXA) at lumbar spine and femoral neck. The patients with osteoporosis were treated with vitamin K2 (glakay 15 mg) (group 1) or vitamin D3 with calcium carbonate (group 2). The patients without osteoporosis was observed without any treatment (group 3). After one year, follow-up BMD was performed in all patients. RESULTS: Of 83 patients, 44 patients (53.0%) had osteoporosis and 39 patients (47.0%) had not. In group 1 (N=28), vitamin K2 treatment significantly increased BMD at femoral neck (-3.2+/-0.4 vs 2.6+/-0.6, p0.05). In group 2 (N=16), there was significant increase in BMD at femoral neck (-3.0+/-0.6 vs -2.5+/-0.8, p0.05). Between group 1 and 2, there was no significant difference in BMD change. In group 3, BMD decreased at femoral neck (-1.3+/-0.2 vs -1.5+/-0.2) and lumbar spine (-0.8+/-0.2 vs -1.0+/-0.2) during follow-up period. CONCLUSION: Vitamin K2 (Menatetrenone(R)) is effective in treating osteoporosis at femoral neck and its effectiveness is s imilar with that of using vitamin D3 with calcium carbonate.