Methylglyoxal activates osteoclasts through JNK pathway leading to osteoporosis

Kwan Ming Lee, Cheuk Yan Lee, Ge ZHANG, Aiping LYU, Kevin K M YUE*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Diabetes mellitus is characterized by chronic hyperglycemia and its diverse complications. Hyperglycemia is associated with inflammatory responses in different organs, and diabetic patients have a higher risk of bone fracture due to increased bone weakness. Methylglyoxal, a reactive advanced glycation end product precursor, is known to have increased level in diabetic patients. The accumulation of methylglyoxal promotes inflammation and it may play a role in diabetes related osteoporosis. In this study, therefore, the underlying mechanism of methylglyoxal on osteoporosis was studied using both animal and cell models. In the animal model, rats were treated with either methylglyoxal or saline as control. In the cell model, the macrophage RAW264.7 was treated with methylglyoxal or vehicle control. Following the treatment, animal samples were harvested for micro-CT and real-time polymerase chain reaction analyses. Cell samples were harvested for MTT assay, RT-PCR, and Western Blotting analyses. In both animals and cell cultures, methylglyoxal was shown to induce osteoclastogenesis by increased gene expression of osteoclast bone biomarkers CTSK, OSCAR and TRACP5. Furthermore, in methylglyoxal-treated macrophages activation of the c-Jun N-terminal kinases signaling pathway was observed, and inhibition of JNK activities resulted in down-regulation of osteoclast biomarkers gene expressions. Our results therefore suggested that methylglyoxal may contribute to the progression of diabetes-related osteoporosis and imbalanced bone remodeling through JNK pathway in osteoclasts.

Original languageEnglish
Pages (from-to)147-154
Number of pages8
JournalChemico-Biological Interactions
Volume308
DOIs
Publication statusPublished - 1 Aug 2019

Scopus Subject Areas

  • Toxicology

User-Defined Keywords

  • Diabetes
  • Methylglyoxal
  • Osteoclast
  • Osteoporosis
  • Pathways

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