Mohammad Osama H, Yang Shuaijie, Ji Wei, Ma Hongdong, Tao Ran
Department of Orthopaedics, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, China.
Department of Orthopaedics, Nantong Haimen Hospital of TCM, Nantong, 226100, China.
Sci Rep. 2025 Aug 12;15(1):29566. doi: 10.1038/s41598-025-15165-8.
Diabetic osteoporosis (DO) is a metabolic bone disorder associated with diabetes mellitus. It is characterized by reduced bone mass, alterations in bone tissue structure as observed under microscopy, increased susceptibility to fractures, and represents one of the complex manifestations of diabetes mellitus in the skeletal system. Hence, it is necessary to prevent and treat DO by enhancing research on its pathogenesis and thereby improving the existing treatment approaches. To explore the mechanism by which curcumin regulates mitochondrial oxidative stress in osteoblasts for treatment of DO via Sirt3/FoxO3a pathway. Firstly, a high-glucose culture model of mouse osteoblast (MC3T3-E1) was established. On this basis, Western Blot and SiRNA techniques were employed to explore the effects of curcumin on the related proteins of SIRT3/FoxO3a, antioxidant enzymes, and mitochondrial function within cells, as well as the osteogenic differentiation of osteoblasts. Eventually, a rat model of diabetic osteoporosis was constructed, and the role of curcumin in regulating the SIRT3/FoxO3a signal to scavenge oxidative stress and restore bone structural integrity in vivo was investigated. The high glucose microenvironment significantly inhibited the cell viability of MC3T3-E1 cells, decreased the level of intracellular antioxidant enzymes, and altered the mitochondrial membrane potential and structure. Curcumin can reverse the mitochondrial oxidative stress damage of MC3T3-E1 and enhance the osteogenic differentiation capacity of cells by activating the SIRT3/FoxO3a pathway. The beneficial effects of curcumin were abolished upon SIRT3 silencing, suggesting that SIRT3/FoxO3a is the principal pathway through which curcumin modulates cellular functions. Based on a rat model of DO, curcumin increased the level of SIRT3 and enhanced bone mineral density and trabecular number in a dose-dependent manner. Curcumin reduces mitochondrial oxidative stress damage through activation of the SIRT3/FoxO3a signaling pathway to improve diabetic osteoporosis.
糖尿病性骨质疏松症（DO）是一种与糖尿病相关的代谢性骨病。其特征为骨量减少、显微镜下观察到的骨组织结构改变、骨折易感性增加，是糖尿病在骨骼系统中的复杂表现之一。因此，有必要通过加强对其发病机制的研究来预防和治疗DO，从而改进现有的治疗方法。为了探究姜黄素通过Sirt3/FoxO3a通路调节成骨细胞线粒体氧化应激以治疗DO的机制。首先，建立小鼠成骨细胞（MC3T3-E1）的高糖培养模型。在此基础上，采用蛋白质免疫印迹法（Western Blot）和小干扰RNA（SiRNA）技术，探究姜黄素对细胞内SIRT3/FoxO3a相关蛋白、抗氧化酶、线粒体功能以及成骨细胞成骨分化的影响。最终，构建糖尿病性骨质疏松大鼠模型，研究姜黄素在体内调节SIRT3/FoxO3a信号以清除氧化应激并恢复骨结构完整性中的作用。高糖微环境显著抑制MC3T3-E1细胞的活力，降低细胞内抗氧化酶水平，改变线粒体膜电位和结构。姜黄素可逆转MC3T3-E1的线粒体氧化应激损伤，并通过激活SIRT3/FoxO3a通路增强细胞的成骨分化能力。沉默SIRT3后，姜黄素的有益作用消失，表明SIRT3/FoxO3a是姜黄素调节细胞功能的主要途径。基于DO大鼠模型，姜黄素可提高SIRT3水平，并以剂量依赖方式增加骨密度和骨小梁数量。姜黄素通过激活SIRT3/FoxO3a信号通路减轻线粒体氧化应激损伤，从而改善糖尿病性骨质疏松症。
