Activity of Parathyroid Hormone Receptor Genes in Ligamentum Flavum Biopsies of Patients with Spinal Canal and Dural Sac Stenosis at the Lumbar Level
https://doi.org/10.29413/ABS.2020-5.6.13
Abstract
Parathyroid hormone receptors PTH1R and PTH2R are poorly studied in the pathology of the vertebral column and may be involved in both ectopic ossification of the vertebral ligaments and fibrous growth of the extracellular matrix, as well as in other unknown processes occurring in the pathological focus.
Aim. To study the expression of genes encoding parathyroid hormone receptors in intraoperative Ligamentum flavum samples of patients with stenosis of the spinal canal and the lumbar dural sac of the spine and to assess the correlation with the expression of other genes active in connective tissue in conditions of developing pathology.
Materials and methods. Studies of the Ligamentum flavum were performed in 33 patients (17 women, 16 men) with stenotic processes of the spinal canal and dural sac of the lumbar spine. RNA was isolated from the biopsies using Qiagen reagents (Germany). Then reverse transcription was performed. cDNA was used for setting up a polymerase chain reaction (Promega Reagents, USA) using a CFX96 thermal cycler (Biorad, USA) with specially selected specific primers.
Results. The expression of genes encoding parathyroid hormone receptors PTH1R and PTH2R was detected and evaluated for the first time in intraoperative Ligamentum flavum samples of patients with spinal canal and dural sac stenosis, and their relationship with the activity of genes encoding estradiol receptors (ESR1 and ESR2) and FGFR3 was revealed. For the first time, common features of PTH1R and PTH2R gene expression, as well as their differences, were revealed. It is proved that the intensity of expression of parathyroid hormone receptors in intraoperative Ligamentum flavum biopsies does not depend on age, gender, or the presence of bone and cartilage nodes according to MRI results. The interdependence of differential changes in the expression of genes of the receptor apparatus involved in the metabolism of Ligamentum flavum tissues was revealed.
About the Authors
L. V. RodionovaRussian Federation
Cand. Sc. (Biol.), Head of the Laboratory of Cell Pathophysiology and Biochemistry; Teaching Assistant at the Department of Clinical Laboratory Medicine
Bortsov Revolyutsii str. 1, Irkutsk 664003, Russian Federation
Yubileyniy 100, Irkutsk 664049, Russian Federation
L. G. Samoilova
Russian Federation
Junior Research Officer at the Laboratory of Cell Pathophysiology and Biochemistry
Bortsov Revolyutsii str. 1, Irkutsk 664003, Russian Federation
V. A. Sorokovikov
Russian Federation
Dr. Sc. (Med.), Professor, Director; Head of the Department of Traumatology, Orthopedy and Neurosurgery
Bortsov Revolyutsii str. 1, Irkutsk 664003, Russian Federation
Yubileyniy 100, Irkutsk 664049, Russian Federation
References
1. Lan X, Gao J, Xu JZ, Liu XM. Treatment of ossification of Ligamentum flavum complicated with lumbar spinal stenosis. Zhongguo Gu Shang. 2017; 30(2): 175-178. doi: 10.3969/j.issn.1003-0034.2017.02.016
2. Ye S, Kwon WK, Bae T, Kim S, Lee JB, Cho TH, et al. CCN5 reduces Ligamentum flavum hypertrophy by modulating the TGF-β pathway. J Orthop Res. 2019; 37(12): 2634-2644. doi: 10.1002/jor.24425
3. Haig AJ, Adewole A, Yamakawa KSJ, Kelemen B, Aagesen AL. The Ligamentum flavum at L4-5: relationship with anthropomorphic factors and clinical findings in older persons with and without spinal disorders. PMR. 2012; 4(1): 23-29.
4. Rahimizadeh A, Soufiani H, Amirzadeh M, Rahimizadeh Sh. Ossification of the Ligamentum flavum of the lumbar spine in Caucasians: case series. J Spine Neurosurg. 2017; 6(5). doi: 10.4172/2325-9701.1000283
5. Mori T, Sakai Y, Kayano M, Matsuda A, Oboki K, Matsumoto K. MicroRNA transcriptome analysis on hypertrophy of Ligamentum flavum in patients with lumbar spinal stenosis. Spine Surg Relat Res. 2017; 1(4): 211-217. doi: 10.22603/ssrr.1.2017-0023
6. Qu X, Chen Z, Fan D, Sun C, Zeng Y, Hou X, et al. Notch signaling pathways in human thoracic ossification of the Ligamentum flavum. J Orthop Res. 2016; 34(8): 1481-1491. doi: 10.1002/jor.23303
7. Le Maitre CL, Richardson SM, Baird P, Freemont AJ, Hoyland JA. Expression of receptors for putative anabolic growth factors in human intervertebral disc: implications for repair and regeneration of the disc. J Pathol. 2005; 207(4): 445-452. doi: 10.1002/path.1862
8. Guo W, Zhang B, Li Y, Duan HQ, Sun C, Xu YQ, et al. Gene expression profile identifies potential biomarkers for human intervertebral disc degeneration. Mol Med Rep. 2017; 16(6): 8665-8672. doi: 10.3892/mmr.2017.7741
9. Hong J, Yan J, Chen J, Li S, Huang Y, Huang Z, et al. Identification of key potential targets for TNF-α/TNFR1-related intervertebral disc degeneration by bioinformatics analysis. Connect Tissue Res. 2020; 26: 1-11. doi: 10.1080/03008207.2020.1797709
10. Severin ES (ed.). Biochemistry: textbook. Moscow: GEOTAR-MED; 2003. (In Russ.)
11. Bringhurst FR. PTH receptors and apoptosis in osteocytes. J Musculoskelet Neuronal Interact. 2002; 2(3): 245-251.
12. Åkesson K, Tenne M, Gerdhem P, Luthman H, McGuigan FE. Variation in the PTH2R gene is associated with age-related degenerative changes in the lumbar spine. J Bone Miner Metab. 2015; 33(1): 9-15. doi: 10.1007/s00774-013-0550-x
13. Galloway TS, Fletcher T, Thomas OJ, Lee BP, Pilling LC, Harries LW. PFOA and PFOS are associated with reduced expression of the parathyroid hormone 2 receptor (PTH2R) gene in women. Chemosphere. 2015; 120: 555-562. doi: 10.1016/j.chemosphere.2014.09.066
14. Bisello A, Manen D, Pierroz DD, Usdin TB, Rizzoli R, Ferrari SL. Agonist-specific regulation of parathyroid hormone (PTH) receptor type 2 activity: structural and functional analysis of PTHand tuberoinfundibular peptide (TIP) 39-stimulated desensitization and internalization. Mol Endocrinol. 2004; 18(6): 1486-1498. doi: 10.1210/me.2003-0487
15. Sato E, Zhang LJ, Dorschner RA, Adase CA, Choudhury BP, Gallo RL. Activation of parathyroid hormone 2 receptor induces decorin expression and promotes wound repair. J Invest Dermatol. 2017; 137(8): 1774-1783. doi: 10.1016/j.jid.2017.03.034
16. Dimitrov EL, Petrus E, Usdin TB. Tuberoinfundibular peptide of 39 residues (TIP39) signaling modulates acute and tonic nociception. Exp Neurol. 2010; 226(1): 68-83. doi: 10.1016/j.expneurol.2010.08.004
17. Tsuda MC, Yeung HM, Kuo J, Usdin TB. Incubation of fear is regulated by TIP39 peptide signaling in the medial nucleus of the amygdala. J Neurosci. 2015; 35(35): 12152-12161. doi: 10.1523/JNEUROSCI.1736-15.2015
18. Dobolyi A, Palkovits M, Usdin TB. The TIP39-PTH2 receptor system: unique peptidergic cell groups in the brainstem and their interactions with central regulatory mechanisms. Prog Neurobiol. 2010; 90(1): 29-59. doi: 10.1016/j.pneurobio.2009.10.017
19. Panda D, Goltzman D, Jüppner H, Karaplis AC. TIP39/parathyroid hormone type 2 receptor signaling is a potent inhibitor of chondrocyte proliferation and differentiation. Am J Physiol Endocrinol Metab. 2009; 297(5): E1125-E1136. doi: 10.1152/ajpendo.00254.2009
20. Bagó AG, Dimitrov E, Saunders R, Seress L, Palkovits M, Usdin TB, et al. Parathyroid hormone 2 receptor and its endogenous ligand tuberoinfundibular peptide of 39 residues are concentrated in endocrine, viscerosensory and auditory brain regions in macaque and human. Neuroscience. 2009; 162(1): 128-147. doi: 10.1016/j.neuroscience.2009.04.054
21. Dimitrov EL, Kuo J, Kohno K, Usdin TB. Neuropathic and inflammatory pain are modulated by tuberoinfundibular peptide of 39 residues. Proc Natl Acad Sci USA. 2013; 110(32): 13156-13161. doi: 10.1073/pnas.1306342110
22. Rodionova LV, Samoilova LG, Shurygina IA, Sklyarenko OV, Zhivotenko A., Koshkareva ZV, et al. Peculiarities of acetylation reactions in patients with stenosis of spinal canal and dural sac of the lumbar spine, depending on the severity of ossification of the Ligamentum flavum. Pathogenesis.2020; 13(3): 45-52. doi: 10.25557/2310-0435.2020.03.45-52. (In Russ.)
23. Bai M, Yin H, Zhao J, Li Y, Wu Y. miR-182-5p overexpression inhibits chondrogenesis by down-regulating PTHLH. Cell Biol Int. 2019; 43(3): 222-232. doi: 10.1002/cbin.11047
Review
For citations:
Rodionova L.V., Samoilova L.G., Sorokovikov V.A. Activity of Parathyroid Hormone Receptor Genes in Ligamentum Flavum Biopsies of Patients with Spinal Canal and Dural Sac Stenosis at the Lumbar Level. Acta Biomedica Scientifica. 2020;5(6):113-123. (In Russ.) https://doi.org/10.29413/ABS.2020-5.6.13