姜黄素通过抑制RANBP3L基因表达减轻2型糖尿病小鼠的骨质疏松症OA

Objective To investigate the therapeutic mechanism of curcumin for osteoporosis induced by type 2 diabetes mellitus(T2DM).Methods In cultured MC3T3-E1 osteoblasts exposed to high glucose(HG),the effects of curcumin treatment on osteogenic differentiation and mineralization were examined by assessing alkaline phosphatase(ALP)activity and using alizarin red S(ARS)staining.RNA-seq sequencing was used to analyze the transcriptional characteristics of MC3T3-E1 osteoblasts in HG culture after curcumin treatment.In a mouse model of T2DM established by high-fat diet feeding and streptococcal injection,the effects of solvent vehicle,vehicle+RANBP3L knockdown,and RANBP3L knockdown+curcumin treatment on blood lipids,bone microstructure and calcium deposition was evaluated using ELISA,HE staining,and Alizarin red S staining.Osteogenic differentiation ability of mouse femoral tissues were assessed by detecting ALP,RANBP3L,OCN and RANKL expressions using immunohistochemical staining,RT-qPCR and Western blotting,and the changes in the TNF-α/NF-κB pathway were detected with Western blotting.Results Curcumin obviously promoted proliferation and osteogenic differentiation of MC3T3-E1 cells in HG culture and down-regulated cellular expression of RANBP3L protein.In the diabetic mouse models,RANBP3L knockdown significantly improved bone microstructure and blood lipid balance,increased expression levels of osteogenic markers,decreased blood glucose level,and caused inhibition of the TNF-α/NF-κB signaling pathway.The combined treatment with curcumin further reduced RANBP3L expression levels in the bone tissue and significantly enhanced the therapeutic effect.Conclusion Curcumin promotes osteogenesis,alleviates glucose and lipid metabolism disorders,and improves osteoporosis in type 2 diabetic mice possibly by inhibiting TNF-α/NF-κB signaling pathway via suppressing RANBP3L expression.