MicroRNA-425-5p modulates osteoporosis by targeting annexin A2.

BACKGROUND: Studies have shown that the decrease of osteogenic differentiation of bone marrow mesenchymal stem cells (MSC) is an important mechanism of osteoporosis. The object of this study was to explore the role and mechanism of microRNA miR-425-5p in the differentiation of MSC. METHODS: The expression of miR-425-5p in MSC was detected by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Cell proliferation, cell cycle and apoptosis were detected by CCK-8 colorimetry and flow cytometry. The expression of TNF were detected by ELISA. RESULTS: Our data show that MiR-425-5p could modulate TNF-induced cell apoptosis, proliferation, and differentiation. ANXA2 is also the target of miR-425-5p and ANXA2 was involved in TNF-induced MSC cell apoptosis, proliferation, and differentiation. In addition, MiR-425-5p enhanced osteoporosis in mice. CONCLUSION: MiR-425-5p might serve as a potential therapeutic target for the treatment of osteoporosis.

miR-22 represses osteoblast viability with ESR1 presenting a direct target and indirectly inactivating p38 MAPK/JNK signaling.

BACKGROUND: MicroRNAs (miRs) hold critical implications in the modulation of osteogenesis. This work was designed to unravel the underlying regulatory mechanism of miR-22 during osteoblast differentiation. METHODS: Synthetic miR-22 mimics or inhibitors were transfected into preosteoblast MC3T3-E1 cells to regulate miR-22 expression. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and flow cytometry analyses were employed to assess cell proliferation and apoptosis. A quantitative real-time polymerase chain reaction and western blot assays were applied to measure mRNA and protein expression. Alkaline phosphatase activity and alizarin red staining were tested to further analyze cell differentiation. In silico analysis and luciferase reporter assays were utilized to identify the direct binding between miR-22 and its potential target. RESULTS: MTT and flow cytometry analyses showed that miR-22 repressed MC3T3-E1 cell viability and promoted cell apoptosis. By detecting osteogenic-specific molecule expression, alkaline phosphatase activity and alizarin red staining, miR-22 was observed to suppress osteogenic differentiation of MC3T3-E1 cells. In silico analysis and luciferase reporter assays confirmed that ESR1 is a direct target gene of miR-22. In addition, miR-22 expression affected the phosphorylation of p38 mitogen-activated protein kinase and Jun N-terminal kinase expression in MC3T3-E1 cells. CONCLUSIONS: The findings of the present study highlight the functional significance of miR-22 in osteoblast differentiation and suggest its role as a possible therapeutic target in metabolic bone disorders.

Tanshinol Alleviates Osteoporosis and Myopathy in Glucocorticoid-Treated Rats.

Tanshinol is a major water-soluble active component of Salvia miltiorrhiza. In this study, we aimed to investigate whether tanshinol has potential therapeutic effects against glucocorticoid-induced osteoporosis and glucocorticoid-induced myopathy. Ninety-six female Sprague-Dawley rats were randomly assigned to five groups: a control group, a model group, and three model groups treated with 25 or 50 mg/kg of tanshinol, or calcitriol. All model groups received prednisone acetate for 90 days to induce glucocorticoid-induced osteoporosis. Afterwards, all animals underwent a surgical procedure to induce bone defects at the right proximal tibia. Prednisone treatment was stopped after surgery, but tanshinol or calcitriol treatment was continued to the endpoint. At the experimental endpoint, compared to the model group, 25 mg/kg tanshinol could significantly reverse glucocorticoid-induced loss of bone mineral density by 12.5 %, while enhancing mechanical bone strength, causing a significant 11 % increase in trabecular number, and reducing trabecular separation by 28 %. In addition, tanshinol improved the bone microarchitecture and prevented glucocorticoid-induced bone loss by promoting bone formation and inhibiting bone resorption. Moreover, results of bone defect repair and muscle weight measurements revealed that tanshinol accelerated the bone fracture healing process and attenuated muscle atrophy caused by glucocorticoid. Furthermore, qRT-PCR analysis showed a 1-fold upregulation in mRNA levels of transforming growth factor beta and roughly 6-fold increases in vascular endothelial growth factor mRNA expression in calluses from the tanshinol groups. Tanshinol also preserved muscular ubiquitin mRNA levels from glucocorticoid-induced elevation. These findings demonstrate the potential benefits of tanshinol against glucocorticoid-induced osteoporosis and glucocorticoid-induced myopathy, which warrants further investigation in future studies.