Correlation analysis between thyroid function-related Thrβ and Thrsp genes and mechanical properties of Achilles tendon development in rats

doi:10.12307/2023.091

Abstract

Abstract: BACKGROUND: Although thyroid diseases are rarely thought to be related to tendon diseases and tendon tears, increasing evidence has indicated that thyroid diseases are involved in idiopathic tendon diseases in recent years. However, there are few studies on the effects of thyroid function on the development and mechanical properties of Achilles tendon during growth and development.
OBJECTIVE: To clarify the correlation between thyroid hormone receptor beta (Thrβ) and thyroid hormone responsive (Thrsp) related to thyroid function and the mechanical properties and histological morphology of the Achilles tendon and to confirm the potential influence of thyroid function on the development of the Achilles tendon.
METHODS: The expression profiles of developmental genes in Achilles tendon were analyzed by bioinformatics, and Thrβ and Thrsp genes related to thyroid function were identified. Then the mechanical properties of the Achilles tendon of female Sprague-Dawley rats at different growth and development stages (28, 42, 56 and 70 days of age, 6 females at each stage) were measured in a tensile test. Hematoxylin-eosin staining combined with histomorphometry was used for histological evaluation and the expression levels of Thrβ and Thrsp genes were determined by fluorescence quantitative PCR. Finally, correlation analysis was conducted to determine the relationship between Thrβ and Thrsp gene expression levels and mechanical properties and histological morphology of the Achilles tendon.
RESULTS AND CONCLUSION: With the growth and development of rats, the maximum load, maximum tensile length and stiffness of the Achilles tendon did not change significantly after peaking. These mechanical properties of Achilles tendon may be related to the content, type and arrangement of collagen fibers in the tissue. Thrβ and Thrsp gene expression in the Achilles tendon at different growth stages were significantly correlated with the mechanical properties and histological scores of the Achilles tendon. These findings suggest that thyroid hormone plays a potential role in the development of the Achilles tendon and it is expected to offer new therapeutic ideas for the repair of Achilles tendon injury.

Key words: Achilles tendon development, bioinformatics, mechanical property, thyroid function, histological morphology

CLC Number:

Niu Jingwei, Zhang Qingtao, Wang Na, Guan Shuo, Wang Ying. Correlation analysis between thyroid function-related Thrβ and Thrsp genes and mechanical properties of Achilles tendon development in rats[J]. Chinese Journal of Tissue Engineering Research, 2023, 27(11): 1653-1658.

Figures/Tables 9

References

[1] BRENT GA. Tissue-specific actions of thyroid hormone: insights from animal models. Rev Endocr Metab Disord. 2000;1:27-33.
[2] BAY-JEXNSEN A, SLAGBOOM E, CHEN-AN P, et al. Role of hormones in cartilage and joint metabolism: understanding an unhealthy metabolic phenotype in osteoarthritis. Menopause. 2013;20:578-586.
[3] YEN PM. Physiological and molecular basis of thyroid hormone action. Physiol Rev. 2001;81:1097-1142.
[4] BUYUKSIRECI DE, TECER D, BOLAYIR B, et al. Ultrasonographic evaluation of shoulder tendons in patients with Hashimoto’s disease. Int J Rheum Dis. 2020;23:1497-1504.
[5] YAO Z, LI J, WANG X, et al. MicroRNA-21-3p Engineered Umbilical Cord Stem Cell-Derived Exosomes Inhibit Tendon Adhesion. J Inflamm Res. 2020; 13:303-316.
[6] LEE M, MAAHS D. 50 Years Ago in TheJournal ofPediatrics: The Achilles Reflex Time in Thyroid Disorders. J Pediatr. 2020;217:78.
[7] ANWAR S, GIBOFSKY A. Musculoskeletal Manifestations of Thyroid Disease. Rheum Dis Clin North Am. 2010;36:637-646.
[8] OLIVA F, GIAI VIA A, MAFFULLI N. Calcific Tendinopathy of the Rotator Cuff Tendons. Sports Med Arthrosc Rev. 2011;19:237-243.
[9] MILGROM C, NOVACK V, WEIL Y, et al. Risk factors for idiopathic frozen shoulder. Isr Med Assoc J. 2008;10:361-364.
[10] KNOPP W, BOHM M, MCCOY J. Hypothyroidism presenting as tendinitis. Phys Sportsmed. 1997;25:47-55.
[11] PURNELL D, DALY D, LIPSCOMB P. Carpal-tunnel syndrome associated with myxedema. AMA Arch Intern Med. 1961;108:751-756.
[12] GARRITY J, BAHN R. Pathogenesis of graves ophthalmopathy: implications for prediction, prevention, and treatment. Am J Ophthalmol. 2006;142:147-153.
[13] SALVI M, GIRASOLE G, PEDRAZZONI M, et al. Increased serum concentrations of interleukin-6 (IL-6) and soluble IL-6 receptor in patients with Graves’ disease. J Clin Endocrinol Metab. 1996;81:2976-2979.
[14] DIEZ J, HERNANZ A, MEDINA S, et al. Serum concentrations of tumour necrosis factor-alpha (TNF-alpha) and soluble TNF-alpha receptor p 55 in patients with hypothyroidism and hyperthyroidism before and after normalization of thyroid function. Clin Endocrinol (Oxf). 2002;57:515-521.
[15] LIU S, WANG Z, ZHU R, et al. Three Differential Expression Analysis Methods for RNA Sequencing: limma, EdgeR, DESeq2. J Vis Exp. 2021;175:231-234.
[16] HU K. Become Competent in Generating RNA-Seq Heat Maps in One Day for Novices Without Prior R Experience. Methods Mol Biol. 2021;2239:269-303.
[17] MYINT L, HADAVAND A, JAGER L, et al. Comparison of beginning R students’ perceptions of peer-made plots created in two plotting systems: a randomized experiment. J Stat Educ. 2020;28:98-108.
[18] CHEN J, ZHANG E, ZHANG W, et al. Fos Promotes Early Stage Teno-Lineage Differentiation of Tendon Stem/Progenitor Cells in Tendon. Stem Cells Transl Med. 2017;6:2009-2019.
[19] WU T, HU E, XU S, et al. ClusterProfiler 4.0: A universal enrichment tool for interpreting omics data. Innovation (New York, NY). 2021;2:100-141.
[20] TAO Y, DING X, JIN J, et al. Predicted rat interactome database and gene set linkage analysis. Database (Oxford). 2020;2020:165-166.
[21] HORINAKA A, KIM Y, KIMURA A, et al. Changes in the predicted function of the rumen bacterial community of Japanese Black beef cattle during the fattening stages according to Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. J Vet Med Sci. 2021;83:1098-1106.
[22] PENG W, ZHOU X, GAO Y, et al. Effect of Access Cavity Preparation on Dentin Preservation, Biomechanical Property, and Instrumentation Efficacy: A Micro-Computed Tomographic Study. J Endod. 2022;46:936-940.
[23] OLIVE F, MAFFULLI N, GISSI C, et al. Combined ascorbic acid and T produce better healing compared to bone marrow mesenchymal stem cells in an Achilles tendon injury rat model: a proof of concept study. J Orthop Surg Res. 2019;14: 54.
[24] 徐若蕙,肖小莉,潘家姝,等.苓桂术甘汤通过Thrsp-Srebp1通路改善高脂饮食诱导的大鼠脂肪变性[J].中华中医药杂志,2021,36(6):3262-3266.
[25] QIU C, LIU S, HONG Y, et al. Molecular characterization of thyroid hormone receptor beta from Schistosoma japonicum and assessment of its potential as a vaccine candidate antigen against schistosomiasis in BALB/c mice. Parasites Vectors. 2012;5:172.
[26] PEREIRA L, PERUCELLI F, SOUZA E, et al. Influence of cervical margin relocation with direct restorative materials on the marginal integrity of CAD-CAM composite inlays. Am J Dent. 2022;35:30-36.
[27] SAHMARAN T, GULTEKIN S. Least Significant Changes and Reproducibility of 131I Uptake Tes. Health Phys. 2021;120:316-320.
[28] ZHANG W, PENG W, ZHAO M, et al. Expression, purification and preliminary crystallographic analysis of human thyroid hormone responsive protein. Acta Crystallogr F Struct Biol Commun. 2011;67:941-946.
[29] HARVIE P, POLLARD TC, CARR AJ. Calcific tendinitis: natural history and association with endocrine disorders. J Shoulder Elbow Surg. 2017;16:169-173.
[30] PAJEK M, AVBELJ STEFANIJA M, TREBUSAK PODKRAJSEK K, et al. Hypercholesterolemia in Two Siblings with Resistance to Thyroid Hormones Due to Disease-Causing Variant in Thyroid Hormone Receptor (THRB) Gene. Medicina (Kaunas). 2020;56:699.