Document Type : Original Article

Authors

Department of Biology, Faculty of Sciences, Central Tehran Branch, Islamic Azad University, Tehran, Iran

Abstract

Background: Diabetes is a common disease affecting majority of populations worldwide. Diabetes is characterized by high levels of circulating glucose and leads to most microvascular and macro vascular complications. Bone marrow vascular disruption and increased adiposity are also linked to various complications in type II diabetes mellitus. In addition to these complications, type 2 diabetic patients also have fragile bones caused by faulty mineralization. Diabetic osteopathy is one of the diabetes mellitus complications. N-acetyl cysteine as an antioxidant can improve the differentiation process of mesenchymal stem cells into osteoblasts in a high glucose medium.
Methods: Human adipose-derived stem cells were cultured in different glucose concentrations, and MTT checked their proliferation and survival. Osteogenic differentiation of adipose stem cells was analyzed by examining the expression of RUNX2 and osterix genes by real-time polymerase chain reaction. The alkaline phosphatase expression was analyzed after 14 days of differentiation of these cells. N-acetyl cysteine antioxidant was added to the differentiation medium, and its effect was studied on the Adipose stem cells differentiation into osteoblasts.
Results: the finding of the study show N acetyl cysteine has antioxidant effect on the proliferation, survival, and differentiation of adipose stem cells into osteoblasts in a high glucose medium significantly. N-acetyl cysteine improved osteogenic parameters as RUNX2, Osterix, alkaline phosphatase in high glucose culture condition.
Conclusion: Generally, the results of the present study show the protective effects of N-acetyl cysteine on the proliferation, survival, and differentiation of adipose derived stem cells into osteoblasts in a high glucose medium and can be used as an antidiabetic drug in the treatment of osteopathy caused by diabetes.

Graphical Abstract

Antioxidant Effect of N-acetyl Cysteine on the Differentiation Improvement of Human Adipose-Derived Stem Cells in a High-Glucose culture

Keywords

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  1. Petersmann A, Müller-Wieland D, Müller U, Landgraf R, Nauck M, Freckmann G, Heinemann L, Schleicher E. (2019).Definition, Classification and Diagnosis of Diabetes Mellitus, Experimental and Clinical Endocrinology & Diabetes., 127: S1-S7. [Crossref], [Google Scholar], [Publisher]
  2. Kanter J E, Bornfeldt KE. (2016).Impact of Diabetes Mellitus, Arteriosclerosis, Thrombosis, and Vascular Biology., 36: 1049-53. [Crossref], [Google Scholar], [Publisher]
  3. Wu Y Y, Xiao E, Graves D T. (2015).Diabetes mellitus related bone metabolism and periodontal disease, International journal of oral science., 7: 63-72. [Crossref], [Google Scholar], [Publisher]
  4. Komori T. (2019).Regulation of Proliferation, Differentiation and Functions of Osteoblasts by Runx2, International journal of molecular sciences., 20: [Crossref], [Google Scholar], [Publisher]
  5. Ma H, Wang X, Zhang W, Li H, Zhao W, Sun J, Yang M. (2020).Melatonin Suppresses Ferroptosis Induced by High Glucose via Activation of the Nrf2/HO-1 Signaling Pathway in Type 2 Diabetic Osteoporosis, Oxidative medicine and cellular longevity., 2020: 9067610. [Crossref], [Google Scholar], [Publisher]
  6. An Y, Zhang H,  Wang C,  Jiao F,  Xu H, Wang X, Luan W, Ma F, Ni L, Tang X, Liu M.  (2019). Activation of ROS/MAPKs/NF-kappaB/NLRP3 and inhibition of efferocytosis in osteoclast-mediated diabetic osteoporosis, The FASEB Journal., 33: 12515-12527. [Crossref], [Google Scholar], [Publisher]
  7. Xie C, Yi J, Jing Lu J, Nie M, Huang M, Jianfang Rong J, Zhu Z, Chen J, Zhou X, Li B, Chen H. (2018). N-Acetylcysteine Reduces ROS-Mediated Oxidative DNA Damage and PI3K/Akt Pathway Activation Induced by Helicobacter pylori Infection, Oxidative Medicine and Cellular Longevity., 2018: 1874985. [Crossref], [Google Scholar], [Publisher]
  8. Hou, Q.,   Huang Y.,  Liu Y., Yiwen Luo Y.,  Wang B., Deng R. Zhang S, Liu F, Chen D. (2018).Profiling the miRNA-mRNA-lncRNA interaction network in MSC osteoblast differentiation induced by (+)-cholesten-3-one, BMC Genomics., 19: 783. [Google Scholar]
  9. Wei J, Shimazu J, Makinistoglu M, MauriziA, Kajimura D, Zong H, Takarada T, Iezaki T, Pessin J E, Hinoi E, Karsenty G. (2015).Glucose Uptake and Runx2 Synergize to Orchestrate Osteoblast Differentiation and Bone Formation, Cell., 161: 1576-1591. [Crossref], [Google Scholar], [Publisher]
  10. Buranaamnuay K. (2021).The MTT assay application to measure the viability of spermatozoa: A variety of the assay protocols, Open veterinary journal., 11: 251-269. [Crossref], [Google Scholar], [Publisher]
  11. Li W, Zhang S, Liu J, Liu Y, Liang Q. (2019).Vitamin K2 stimulates MC3T3E1 osteoblast differentiation and mineralization through autophagy induction, Mol Med Rep., 19: 3676-3684. [Crossref], [Google Scholar], [Publisher]
  12. Aroda V R, Knowler W C, Crandall J P, Perreault L, Edelstein S L, Jeffries S L, Molitch M E, Pi-Sunyer X, Darwin C, Heckman-Stoddard B M, Temprosa M. (2017).Metformin for diabetes prevention: insights gained from the Diabetes Prevention Program/Diabetes Prevention Program Outcomes Study, Diabetologia., 60: 1601-1611. [Crossref], [Google Scholar], [Publisher]
  13. Jiating L, Buyun J, Yinchang Z. (2019).Role of Metformin on Osteoblast Differentiation in Type 2 Diabetes, BioMed Research International., 2019: 9203934. [Crossref], [Google Scholar], [Publisher]
  14. Watanabe A, de Almeida M O, Deguchi Y, Kozuka R, Arruda C, Berretta A A, Bastos J K, Woo J T, Yonezawa T.(2021).Effects of Baccharin Isolated from Brazilian Green Propolis on Adipocyte Differentiation and Hyperglycemia in ob/ob Diabetic Mice, International Journal of Molecular Sciences., 22: [Crossref], [Google Scholar], [Publisher]
  15. Alnahdi A, John A, Raza H. (2019). N-acetyl cysteine attenuates oxidative stress and glutathione-dependent redox imbalance caused by high glucose/high palmitic acid treatment in pancreatic Rin-5F cells, PLoS One., 14: e0226696. [Crossref], [Google Scholar], [Publisher]
  16. Azpiazu D, Gonzalo S, Villa-Bellosta R. (2019).Tissue Non-Specific Alkaline Phosphatase and Vascular Calcification: A Potential Therapeutic Target, Current cardiology reviews., 15: 91-95. [Crossref], [Google Scholar], [Publisher]
  17. Aung M,   Amin S,  Gulraiz A,  Gandhi F,  Escobar J,   Malik B. (2020).The Future of Metformin in the Prevention of Diabetes-Related Osteoporosis, Cureus., 12: e10412. [Google Scholar], [Publisher]
  18. Sun Y,   Zhu Y,   Liu X,   Chai Y,  Jia Xu J. (2020).Morroniside attenuates high glucose-induced BMSC dysfunction by regulating the Glo1/AGE/RAGE axis, Cell Proliferation., 53: e12866. [Crossref], [Google Scholar], [Publisher]
  19. Wang Y, Shi P,  Chen Q,   Huang Z,  Zou D,  Zhang J, Gao X, Lin Z. (2019).Mitochondrial ROS promote macrophage pyroptosis by inducing GSDMD oxidation Journal of molecular cell biology., 11: 1069-1082. [Crossref], [Google Scholar], [Publisher]
  20. Nogueira G B, Punaro G R, Oliveira C S, Maciel F R, Fernandes T O, Lima D Y, Rodrigues A M, Mouro M G, Araujo S R, Higa E M. (2018). N-acetylcysteine protects against diabetic nephropathy through control of oxidative and nitrosative stress by recovery of nitric oxide in rats, Nitric Oxide., 78: 22-31. [Crossref], [Google Scholar], [Publisher]
  21. Tian Y, Song W, Xu D, Chen X, Li X, Zhao Y. (2020). Autophagy Induced by ROS Aggravates Testis Oxidative Damage in Diabetes via Breaking the Feedforward Loop Linking p62 and Nrf2, Oxidative Medicine and Cellular Longevity., 2020: 7156579. [Crossref], [Google Scholar], [Publisher]