The inhibition of PINK1/Drp1-mediated mitophagy by hyperglycemia leads to impaired osteoblastogenesis in diabetes

The inhibition of PINK1/Drp1-mediated mitophagy by hyperglycemia leads to impaired osteoblastogenesis in diabetes

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Summary: Impaired bone quality and increased fracture risk are cardinal features of the skeleton in diabetes mellitus.Hyperglycemia-induced oxidative stress is proposed as a potential underlying mechanism, but the precise pathogenic mechanism remains incompletely understood.In this investigation, osteoblasts under high glucose exhibited heightened levels vista 5 vl5 of reactive oxygen species, impaired mitochondrial membrane potential, and profound inhibition of late-stage osteoblast differentiation.Further analyses uncovered that high glucose resulted in the downregulation of the PINK1/Drp1 pathway in osteoblasts, consequently leading to impaired mitophagy.

Conversely, the upregulation of PINK1/Drp1 pathway activated mitophagy, which restored the differentiation capacity of osteoblasts.Notably, in an STZ-induced diabetic mouse model, BMP9 upregulated the expression of PINK1/Drp1 in the bone tissue, leading to an improvement in medline guardian toilet safety rails bone quality and bone mineral density.These findings suggest that the PINK1/Drp1 pathway might be a potential therapeutic target to enhance osteogenic differentiation and treat diabetic osteoporosis.