Factors of local conversion of iodothyronines correlate with indicators of hormonal, biochemical, and hematological profiles in patients with spinal canal and dural sac stenosis of the lumbar spine

In order to find out the mechanisms of pathogenesis of degenerative-dystrophic diseases of the spine, it is of particular interest to search for body parameters which are directly or indirectly interrelated with the key factors of peripheral conversion of nidus iodothyronines and constitute a system of network interactions, affecting metabolic indicators at the local and systemic level.
The aim. To search for correlations of local key factors of peripheral conversion of Ligamentum flavum iodothyronines with indicators of biochemical, hematological and hormonal blood profiles of patients with stenosing processes of the spinal canal and dural sac in the lumbar spine.
Materials and methods. 33 patients (15 males, 18 females) with stenosing processes of the spinal canal and dural sac in the lumbar spine were examined (mean age – 45.73 ± 1.95 years). The expression of deiodinase genes and other candidate genes was determined in Ligamentum flavum biopsies collected during surgical treatment. Biochemical, hematological and hormonal parameters were determined in peripheral blood. The resulting data array was processed in order to find correlations between the parameters of systemic and local metabolism.
Results. The relationships of deiodinases with the expression of GDF5, MMP1, MMP3 and TIMP1 in Ligamentum flavum (p < 0.05) were found. Of the hormonal profile of the blood serum, the most significant indicators were thyreotropin, free triiodothyronine and thyroperoxidase antibodies. In the biochemical profile, levels of direct bilirubin, total cholesterol, HDL and LDL cholesterol and triglycerides changed along with the expression of deiodinases. Correlative relationships with the expression of deiodinases were found for the following hematological analytes of whole peripheral blood: hemoglobin, mean corpuscular hemoglobin concentration, numbers of granulocytes, lymphocytes, eosinophils, monocytes, band neutrophils, red cell distribution width and platelet crit. The data obtained indicate the involvement of peripheral conversion factors in the pathogenetic process and provide information to form a new view on the pathogenesis of degenerative-dystrophic processes in the Ligamentum flavum of patients with stenosing processes of the spinal canal and the dural sac in the lumbar spine.

1. Rodionova LV, Samoilova LG, Nevezhina AV, Shurygina IA. Expression of deiodinase genes in intraoperative samples of Ligamentum flavum in patients with stenotic processes of the spinal canal and dural sac on the lumbar spine. Acta biomedica scientifica. 2019; 4(6): 20-25. (In Russ.). doi: 10.29413/ABS.2019-4.6.3

2. Mokhort EG. The role of selenium in the pathogenesis of iodine deficiency. Medical Journal. 2003; 3: 88-94. (In Russ.).

3. Rodionova LV, Samoilova LG, Bogorodskaya SL, Gorokhova VG, Sorokovikov VA. Molecular genetic studies of intraoperative Ligamentum flavum bioptates of patients with spinal canal stenosis. Acta biomedica scientifica. 2020; 5(6): 144-150. (In Russ.). doi: 10.29413/ABS.2020-5.6.16

4. Rodionova LV, Samoilova LG, Shurygina IA, Sklyarenko OV, Zhivotenko AP, Koshkareva ZV, et al. Characteristics of acetylation reactions in patients with stenosing process of the lumbar spinal canal and dural sac depending on severity of Ligamentum flavum ossification. Pathogenesis. 2020; 18(3): 45-52. (In Russ.). doi: 10.25557/2310-0435.2020.03.45-52

5. National Center for Biotechnological Information. URL: https://ncbi.nlm.nih.gov [date of access: 09.10.2022].

6. Zhong ZM, Chen JT, Zhang Y, Zha DS, Lin ZS, Zhao CY, et al. Growth/differentiation factor-5 induces osteogenic differentiation of human Ligamentum flavum cells through activation of ERK1/2 and p38 MAPK. Cell Physiol Biochem. 2010; 26(2): 179-186. doi: 10.1159/000320526

7. Rodionova LV, Samoilova LG, Sorokovikov VA. Activity of genes of matrix metalloproteinases and their inhibitors in the Ligamentum flavum of patients with stenosing processes in spinal canal and dural sac. Acta biomedica scientifica. 2021; 6(6-2): 58-72. (In Russ.). doi: 10.29413/ABS.2021-6.6-2.7

8. Hsu HT, Yue CT, Teng MS, Tzeng IS, Li TC, Tai PA, et al. Immuohistochemical score of matrix metalloproteinase-1 may indicate the severity of symptomatic cervical and lumbar disc degeneration. Spine J. 2020; 20(1): 124-137. doi: 10.1016/j.spinee.2019.08.004

9. Cao J, Zucker S. Biology and chemistry of matrix metalloproteinases (MMPs). URL: http://www.abcam.com/index.html?pageconfig=resource&rid=11034 [date of access: 26.12.2011].

10. Xue M, March L, Sambrook PN, Jackson ChJ. Differential regulation of matrix metalloproteinase 2 and matrix metalloproteinase 9 by activated protein C relevance to inflammation in rheumatoid arthritis. Arthritis Rheumatism. 2007; 56(9): 2864-2874. doi: 10.1002/art.22844

11. Fernandez CA, Butterfield C, Jackson G, Moses MA. Functional uncoupling of the enzymatic and angiogenic inhibitory activities of tissue inhibitor of metalloproteinase-2 (TIMP-2). J Biol Chemistry. 2003; 278(42): 40989-40995. doi: 10.1074/jbc.M306176200

12. Ruf J, Carayon P. Structural and functional aspects of thyroid peroxidase. Arch Biochem Biophys. 2006; 445(2): 269-277. doi: 10.1016/j.abb.2005.06.023

13. Burkutbaeva MM, Burkutbaeva LM, Lebedeva EN. Mechanisms of action of non-classical thyroid hormones. Mezhdunarodnyy studencheskiy nauchnyy vestnik. 2015; 2-3; URL: https://eduherald.ru/ru/article/view?id=12262 [date of access: 06.10.2022]. (In Russ.).