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Article

Uncarboxylated osteocalcin inhibits high glucose-induced ROS production and stimulates osteoblastic differentiation by preventing the activation of PI3K/Akt in MC3T3-E1 cells

  • Authors:
    • Jingli Liu
    • Jianhong Yang
  • View Affiliations / Copyright

    Affiliations: College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, P.R. China
  • Pages: 173-181
    |
    Published online on: November 17, 2015
       https://doi.org/10.3892/ijmm.2015.2412
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Abstract

Uncarboxylated osteocalcin, an osteoblast-derived protein, plays an important role in the regulation of glucose metabolism. It has previously been demonstrated that high glucose levels inhibit osteoblast proliferation and differentiation. However, the mechanisms through which uncarboxylated osteocalcin regulates osteoblast proliferation and differentiation under high glucose conditions remain unclear. Thus, in the present study, we aimed to examine the effects of uncarboxylated osteocalcin on the proliferation and differentiation of MC3T3-E1 cells under high glucose conditions. We demonstrated that high glucose levels induced the production of reactive oxygen species (ROS) in MC3T3-E1 cells, and this production was inhibited by treatment with uncarboxylated osteocalcin and N-acetyl-L-cysteine (NAC), a ROS scavenger. In addition, we found that uncarboxylated osteocalcin reduced high glucose‑induced oxidative stress and increased the mRNA expression of the osteogenic markers, runt-related transcription factor 2 (Runx2), osterix and osteocalcin, as well as the formation of mineralized nodules; it also inhibited adipogenic differentiation, as shown by a decrease in the mRNA expression of the adipogenic markers, peroxisome proliferator‑activated receptor γ (PPARγ), adipocyte fatty acid-binding protein (adipocyte protein 2; aP2) and fatty acid synthase (FAS), and reduced lipid drop accumulation. Furthermore, we found that uncarboxylated osteocalcin inhibited PI3K/Akt signaling which was induced by ROS and facilitated the osteogenic differentiation of MC3T3-E1 cells under high glucose conditions. Taken together and to the best of ou knowledge, our results demonstrate for the first time that uncarboxylated osteocalcin inhibits high glucose-induced ROS production and stimulates osteoblastic differentiation by inhibiting the activation of PI3K/Akt in MC3T3-E1 cells. Therefore, we suggest that uncarboxylated osteocalcin may be a potential therapeutic agent for diabetes-related osteoporosis.
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Copy and paste a formatted citation
Spandidos Publications style
Liu J and Yang J: Uncarboxylated osteocalcin inhibits high glucose-induced ROS production and stimulates osteoblastic differentiation by preventing the activation of PI3K/Akt in MC3T3-E1 cells. Int J Mol Med 37: 173-181, 2016.
APA
Liu, J., & Yang, J. (2016). Uncarboxylated osteocalcin inhibits high glucose-induced ROS production and stimulates osteoblastic differentiation by preventing the activation of PI3K/Akt in MC3T3-E1 cells. International Journal of Molecular Medicine, 37, 173-181. https://doi.org/10.3892/ijmm.2015.2412
MLA
Liu, J., Yang, J."Uncarboxylated osteocalcin inhibits high glucose-induced ROS production and stimulates osteoblastic differentiation by preventing the activation of PI3K/Akt in MC3T3-E1 cells". International Journal of Molecular Medicine 37.1 (2016): 173-181.
Chicago
Liu, J., Yang, J."Uncarboxylated osteocalcin inhibits high glucose-induced ROS production and stimulates osteoblastic differentiation by preventing the activation of PI3K/Akt in MC3T3-E1 cells". International Journal of Molecular Medicine 37, no. 1 (2016): 173-181. https://doi.org/10.3892/ijmm.2015.2412
Copy and paste a formatted citation
x
Spandidos Publications style
Liu J and Yang J: Uncarboxylated osteocalcin inhibits high glucose-induced ROS production and stimulates osteoblastic differentiation by preventing the activation of PI3K/Akt in MC3T3-E1 cells. Int J Mol Med 37: 173-181, 2016.
APA
Liu, J., & Yang, J. (2016). Uncarboxylated osteocalcin inhibits high glucose-induced ROS production and stimulates osteoblastic differentiation by preventing the activation of PI3K/Akt in MC3T3-E1 cells. International Journal of Molecular Medicine, 37, 173-181. https://doi.org/10.3892/ijmm.2015.2412
MLA
Liu, J., Yang, J."Uncarboxylated osteocalcin inhibits high glucose-induced ROS production and stimulates osteoblastic differentiation by preventing the activation of PI3K/Akt in MC3T3-E1 cells". International Journal of Molecular Medicine 37.1 (2016): 173-181.
Chicago
Liu, J., Yang, J."Uncarboxylated osteocalcin inhibits high glucose-induced ROS production and stimulates osteoblastic differentiation by preventing the activation of PI3K/Akt in MC3T3-E1 cells". International Journal of Molecular Medicine 37, no. 1 (2016): 173-181. https://doi.org/10.3892/ijmm.2015.2412
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