Markers of bone tissue remodeling in case of bone metabolism disorders

Authors

DOI:

https://doi.org/10.26641/1997-9665.2024.2.73-77

Keywords:

bone tissue, osteoblasts, osteoclasts, hyperglycemia, RANKL, osteopontin, metabolism.

Abstract

Introduction. Diabetes mellitus belongs to the group of debilitating metabolic diseases, as evidenced by the changes that occur in the organs and systems of the body. Today, experimental diabetology is of great importance for studying the pathogenesis of this disease. Functional and physiological restructuring of bone tissue occurs due to balanced processes of modeling and remodeling that run in parallel to each other. The article presents the results of the study of changes in biochemical markers of bone metabolism in rats with persistent hyperglycemia. The aim of the study was to determine the relationship between the level of metabolic changes in osteogenic cells and the secretion of bone remodeling markers in rat bones under conditions of experimental hyperglycemia. Methods. The study was conducted on 36 white laboratory rats. The rats were induced into a state of chronic hyperglycemia by a single intraperitoneal injection of alloxan dihydrate solution at a dose of 150 mg/kg body weight in 0.9% sodium chloride solution. The blood glucose level was determined by the glucose oxidase method. The level of glucose in urine was determined by the rapid method using test strips. The rats were withdrawn from the experiment every 30 days by decapitation under light thiopental-sodium anesthesia. The duration of the experiment was 60 days. Femurs were removed for the study. The study of osteogenic cells was performed by immunohistochemical analysis (IHC). The expression of osteopontin and RANKL in bone tissue was analyzed using a light microscope and the Allred scale. Statistical processing of the study results was performed using the Statistica v.10 program. Results. Persistent hyperglycemia leads to the development of destructive changes in osteogenic cells of the experimental group. These changes were manifested in a slowdown in bone remodeling, inhibition of osteogenic cells and their differentiation, which in turn leads to impaired growth and bone mineral density. In this case, in the rats of the experimental group, significant changes occurred already on day 30 of observation. Conclusion. It has been proved that in rats with a constantly high level of hyperglycemia there is a marked decrease in bone remodeling processes.

References

  1. Zhang X, Krishnamoorthy S, Tang CT, Hsu WW, Li GH, Sing CW, Tan KC, Cheung BM, Wong IC, Kung AW, Cheung CL. Association of Bone Mineral Density and Bone Turnover Markers with the Risk of Diabetes: Hong Kong Osteoporosis Study and Mendelian Randomization. J Bone Miner Res. 2023;38(12):1782-1790. doi: 10.1002/jbmr.4924.
  2. Hofbauer LC, Busse B, Eastell R, et al. Bone fragility in diabetes: novel concepts and clinical implications. Lancet Diabetes Endocrinol. 2022;10(3):207–220.
  3. Capulli M, Ponzetti M, Maurizi A, et al. A complex role for lipocalin 2 in bone metabolism: global ablation in mice induces osteopenia caused by an altered energy metabolism. J Bone Miner Res. 2018;33(6):1141–1153.
  4. Cheung CL, Tan KCB, Kung AWC. Cohort profile: the Hong Kong osteoporosis study and the follow-up study. Int J Epidemiol. 2018;47(2):397–398f.
  5. Chau YP, Au PCM, Li GHY, et al. Serum metabolome of coffee consumption and its association with bone mineral density: the Hong Kong osteoporosis study. J Clin Endocrinol Metab. 2020;105(3):dgz210.
  6. Li GH, Cheung CL, Au PC, Tan KC, Wong IC, Sham PC. Positive effects of low LDL-C and statins on bone mineral density: an integrated epidemiological observation analysis and Mendelian randomization study. Int J Epidemiol. 2020;49(4):1221–1235.
  7. Cheung CL, Sing CW, Lau WCY, et al. Treatment with direct oral anticoagulants or warfarin and the risk for incident diabetes among patients with atrial fibrillation: a population-based cohort study. Cardiovasc Diabetol. 2021;20(1):71.
  8. Luk AOY, Ke C, Lau ESH, et al. Secular trends in incidence of type 1 and type 2 diabetes in Hong Kong: a retrospective cohort study. PLoS Med. 2020;17(2):e1003052.
  9. Morris JA, Kemp JP, Youlten SE, et al. An atlas of genetic influences on osteoporosis in humans and mice. Nat Genet. 2019;51(2):258–266.
  10. Mahajan A, Spracklen CN, Zhang W, et al. Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation. Nat Genet. 2022;54(5):560–572.
  11. Liu Z, Asuzu P, Patel A, Wan J, Dagogo-Jack S. Association of bone mineral density with prediabetes risk among African-American and European-American adult offspring of parents with type 2 diabetes. Front Endocrinol (Lausanne). 2022;13:1065527.
  12. Matsumoto T, Endo I. RANKL as a target for the treatment of osteoporosis. J Bone Miner Metab. 2021 Jan;39(1):91-105.
  13. Ming J, Cronin SJF, Penninger JM. Targeting the RANKL/RANK/OPG Axis for Cancer Therapy. Front Oncol. 2020 Aug 7;10:1283.
  14. Győri DS, Mócsai A. Osteoclast Signal Transduction During Bone Metastasis Formation. Front Cell Dev Biol. 2020 Jun 19;8:507.
  15. Wu M, Ai W, Chen L, Zhao S, Liu E. Bradykinin receptors and EphB2/EphrinB2 pathway in response to high glucose-induced osteoblast dysfunction and hyperglycemia–induced bone deterioration in mice. Int J Mol Med. 2019 Apr;43(4):1920.
  16. Guo H, Wang C, Jiang B, et al. Association of insulin resistance and beta-cell function with bone turnover biomarkers in dysglycemia patients. Front Endocrinol (Lausanne). 2021;12:554604.
  17. Starup-Linde J, Lykkeboe S, Handberg A, et al. Glucose variability and low bone turnover in people with type 2 diabetes. Bone. 2021;153:116159.
  18. Frost M, Balkau B, Hatunic M, Konrad T, Mingrone G, Hojlund K. The relationship between bone turnover and insulin sensitivity and secretion: cross-sectional and prospective data from the RISC cohort study. Bone. 2018;108:98–105.
  19. Picke AK, Campbell G, Napoli N, Hofbauer LC, Rauner M. Update on the impact of type 2 diabetes mellitus on bone metabolism and material properties. Endocr Connect. 2019 Mar 1;8(3):R55-R70.
  20. Wang L, Li T, Liu J, Wu X, Wang H, Li X, et al. Association between glycosylated hemoglobin A1c and bone biochemical markers in type 2 diabetic postmenopausal women: a cross-sectional study. BMC Endocr Disord. 2019 Mar 12;19(1):31.

Published

2024-07-30

How to Cite

Ponyrko , A., & Bumeіster V. (2024). Markers of bone tissue remodeling in case of bone metabolism disorders. Морфологія / Morphologia / Morfologìâ, 18(2), 73–77. https://doi.org/10.26641/1997-9665.2024.2.73-77

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