The inhibition of PINK1/Drp1-mediated mitophagy by hyperglycemia leads to impaired osteoblastogenesis in diabetes
2024

How High Sugar Affects Bone Growth in Diabetes

publication 10 minutes Evidence: high

Author Information

Author(s): Chen Xiao-jing, Yang Yu-ying, Pan Zheng-can, Xu Jing-zun, Jiang Tao, Zhang Lin-lin, Zhu Ke-cheng, Zhang Deng, Song Jia-xi, Sheng Chun-xiang, Sun Li-hao, Tao Bei, Liu Jian-min, Zhao Hong-yan

Primary Institution: Shanghai Jiao Tong University School of Medicine

Hypothesis

The study investigates whether high glucose levels impair osteoblastogenesis through the inhibition of the PINK1/Drp1-mediated mitophagy pathway.

Conclusion

High glucose levels inhibit osteoblast differentiation by suppressing the PINK1/Drp1-mediated mitophagy pathway, but BMP9 can reverse this effect.

Supporting Evidence

  • High glucose levels led to increased reactive oxygen species and decreased mitochondrial membrane potential in osteoblasts.
  • BMP9 treatment improved osteogenic differentiation and mitochondrial function in high glucose conditions.
  • RNA sequencing revealed downregulation of PINK1 and Drp1 in osteoblasts exposed to high glucose.

Takeaway

When there's too much sugar, it can hurt the cells that help make bones, but a special protein called BMP9 can help fix that.

Methodology

The study used in vitro experiments with MC3T3-E1 cells and in vivo experiments with STZ-induced diabetic mice to assess the effects of high glucose on osteoblast differentiation and mitochondrial function.

Limitations

The precise mechanism of BMP9 activation of the PINK1/Drp1 pathway needs further investigation, and the study did not use osteoblast conditional gene knockout models.

Statistical Information

P-Value

p<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1016/j.isci.2024.111519

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