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

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Abstract：ObjectiveToinvestigatethetherapeuticmechanismof curcuminforosteoporosisinducedbytype2diabetes melitus （T2DM）.Methods Incultured MC3T3-E1osteoblasts exposed toigh glucose （HG），theefectsofcurcumintreatment on osteogenic diferentiationand mineralization were examined by assessing alkaline phosphatase （ALP）activityand using alizarinredS （ARS）staining.RNA-seq sequencingwasused toanalyzethetranscriptionalcharacteristicsofMC3T3-E1 osteoblastsinHGcultureaftercurcumintreatment.InamousemodelofT2DMestablishedbyhigh-fatdietfedingand streptococcalinjection，theeffectsofsolventvehicle，vehicle+RANBP3Lknockdown，andANBP3Lknockdown+curcumin treatmentonbloodlipidsonemicrostructureandcalciumdepositionwasevaluatedusingELIA，HEtainingndAlzarin redSstainingOseogeicereiationbilityofousemoralusreesedbyetecing andRANKLexpressonsusingimmunohistochemicalstainingRT-qCRandWesternblotingandthechangesintheTNF- ⋅α/ NF-kBpathwaywere detected with Westernbloting.ResultsCurcuminobviously promotedproliferationandosteogenic diferentitionofMC3T3-E1cels inHGcultureand down-regulatedcellularexpressionofRANBP3L protein.Inthediabetic mousemodels，RANBP3Lknockdownsignificantlyimprovedbonemicrostructureandbloodlipidbalance，increased expresionlevelsofseogenicmarkersdecreasedloodglucoselevel，andsedinbiionoftheF-/F-igling pathway.Thecombined treatment withcurcumin further reducedRANBP3L expression levelsinthebone tissue and significantlyenhanced the therapeuticefect.Conclusion Curcuminpromotesosteogenesis，alleviatesglucoseandlipid metabolismdisorders，andimprovesosteoporosisintype2diabeticmiceposiblybyinhibitingTNF-/NF-kBsignaling pathway via suppressing RANBP3L expression.

Keywords： curcumin; RANBP3L; type 2 diabetes osteoporosis; mRNA sequencing

2型糖尿病（T2DM）作为一种慢性代谢性疾病，主要特征为胰岛素抵抗以及β细胞功能逐步下降。（剩余16308字）