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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Alkaline Phosphatase, Animals, Blotting, Western, Cell Differentiation, Cell Line, Cell Proliferation, Cell Survival, Core Binding Factor Alpha 1 Subunit, Ephrin-B2, Integrin-Binding Sialoprotein, Mice, Osteogenesis, RNA Interference, RNA, Messenger, RNA, Small Interfering, Real-Time Polymerase Chain Reaction, Receptor, EphB4, Signal Transduction, Tumor Necrosis Factor-alpha.
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Do low concentrations of TNF-α promote osteogenic differentiation via activation of the ephrinB2-EphB4 signalling pathway? Context: Low concentrations of tumour necrosis factor-alpha (TNF-α) have been reported to promote osteogenic differentiation. In this study, a series of in vitro experiments was performed to investigate underlying molecular mechanisms involved. MC3T3-E1 murine preosteoblasts were treated with TNF-α at doses of 0, 0.1 or 1 ng/mL. The ephrinB2-EphB4 signalling pathway was activated using ephrinB2-fc, or inhibited using lentiviruses encoding siRNAs specifically targeting EphB4. Cell proliferation/survival was evaluated using the Cell Counting Kit-8 (CCK-8) assay, and expression levels of Runx2, BSP, ephrinB2 and EphB4 were determined using RT-PCR and Western blotting. ALP activity in these cells was also determined, and mineral nodule formation was evaluated with alizarin red S staining. Low concentrations of TNF-α had no influence on cell proliferation/survival. However, expression levels of Runx2, BSP, ephrinB2 and EphB4, as well as ALP activity and mineral nodule formation, were significantly enhanced in MC3T3-E1 cells treated with low concentrations of TNF-α. Moreover, activation of the ephrinB2-EphB4 signalling pathway by ephrinB2-fc enhanced TNF-α-induced osteogenic differentiation, while down-regulation of EphB4 level reversed the positive effect of TNF-α.
assistant
Low concentrations of TNF-α promoted osteogenic differentiation via activation of the ephrinB2-EphB4 signalling pathway. Final Decision: yes