糖尿病性骨质疏松与脂肪干细胞成骨分化能力损害机制研究进展OA北大核心

Bone complications such as osteoporosis and delayed bone healing caused by long-term hyperglycemia in patients with diabetes mellitus(DM)have become clinical problems that significantly reduce their quality of life.The core mechanism is closely related to the impaired osteogenic differentiation ability of adipose-derived stem cells(ADSCs).In bone tissue engineering,ADSCs are considered as seed cells for bone defect repair due to their minimal invasiveness,rapid proliferation and multi-directional differentiation ability.However,the pathological environment of DM significantly inhibits the osteogenic potential of ADSCs,which affects the treatment efficiency of diabetic bone diseases.Therefore,it is of great significance to explore the underlying mechanism of impaired osteogenic ability of ADSCs in hyperglycemic environment for optimizing the treatment strategy of diabetic bone diseases.This article systematically reviewed and summarized the potential mechanisms of decreased migration ability,reduced proliferation activity,accelerated senescence and apoptosis,and impaired osteogenic differentiation of ADSCs in high glucose environment.High glucose environment can inhibit the expression of osteogenesis-related genes by activating oxidative stress,accumulation of advanced glycation end products,and disrupting Wnt/β-catenin,PI3K/Akt/mTOR,Notch and other key signaling pathways.In addition,DNA methylation in epigenetic modification and non-coding RNA network can jointly silence osteogenic genes.Further elucidation of the above mechanisms not only helps to understand the pathogenesis of diabetic bone diseases,but also provides a direction for the development of intervention strategies.This review aims to promote the application of ADSCs in regenerative medicine for DM management and provide a theoretical basis for further development of strategies for autologous ADSCs repair and treatment of bone defects in DM patients.