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

ABSTRACT: 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 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-

SUBMITTER: Chen XJ 

PROVIDER: S-EPMC11699391 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature