Contribution of methylglyoxal to delayed healing of bone injury in diabetes

  • Authors:
    • Takao Aikawa
    • Hidenori Matsubara
    • Shuhei Ugaji
    • Junichi Shirakawa
    • Ryoji Nagai
    • Seiichi Munesue
    • Ai Harashima
    • Yasuhiko Yamamoto
    • Hiroyuki Tsuchiya
  • View Affiliations

  • Published online on: May 16, 2017     https://doi.org/10.3892/mmr.2017.6589
  • Pages: 403-409
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Patients with diabetes are vulnerable to delayed bone fracture healing or pseudoarthrosis. Chronic sustained hyperglycemia, reactive intermediate derivatives of glucose metabolism, such as methylglyoxal (MGO), and advanced glycation end‑products (AGEs) are implicated in diabetic complications. In the present study, it was examined whether MGO is able to cause disturbed bone healing in diabetes. Diabetes was induced in male mice by injection of streptozotocin (50 mg/kg) for 5 days. A bone defect (1.0‑mm diameter) was created in the left distal femur, and bone repair was assessed from an examination of computed tomography scans. ST2 cells were exposed to MGO (0‑400 µM) to investigate osteoblastic differentiation, cell viability, and damage. Consequently, blood glucose and hemoglobin A1c levels in diabetic mice were determined to be 493±14.1 mg/dl and 8.0±0.05%, respectively. Compared with non‑diabetic control mice, diabetic mice exhibited markedly delayed bone healing, with increased levels of the MGO‑derived AGEs, Nε‑(carboxymethyl)‑lysine and Nδ‑(5‑hydro‑5‑methyl‑4‑imidazolone‑2‑yl)‑ornithine, in the sera and femurs. MGO inhibited the osteoblastic differentiation of ST2 cells in a dose‑dependent manner, and markedly decreased cell proliferation through cytotoxicity. In conclusion, MGO has been demonstrated to cause impaired osteoblastic differentiation and delayed bone repair in diabetes. Therefore, detoxification of MGO may be a potentially useful strategy against bone problems in patients with diabetes.
View Figures
View References

Related Articles

Journal Cover

July 2017
Volume 16 Issue 1

Print ISSN: 1791-2997
Online ISSN:1791-3004

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
APA
Aikawa, T., Matsubara, H., Ugaji, S., Shirakawa, J., Nagai, R., Munesue, S. ... Tsuchiya, H. (2017). Contribution of methylglyoxal to delayed healing of bone injury in diabetes. Molecular Medicine Reports, 16, 403-409. https://doi.org/10.3892/mmr.2017.6589
MLA
Aikawa, T., Matsubara, H., Ugaji, S., Shirakawa, J., Nagai, R., Munesue, S., Harashima, A., Yamamoto, Y., Tsuchiya, H."Contribution of methylglyoxal to delayed healing of bone injury in diabetes". Molecular Medicine Reports 16.1 (2017): 403-409.
Chicago
Aikawa, T., Matsubara, H., Ugaji, S., Shirakawa, J., Nagai, R., Munesue, S., Harashima, A., Yamamoto, Y., Tsuchiya, H."Contribution of methylglyoxal to delayed healing of bone injury in diabetes". Molecular Medicine Reports 16, no. 1 (2017): 403-409. https://doi.org/10.3892/mmr.2017.6589