Pathogenetic features of experimental osteoarthrosis induced by dexamethasone and talc

The aim of the study was to investigate the pathogenesis of experimental osteoarthrosis induced by dexamethasone and talc by examining the structure and defining the morphometric and metabolic features of knee joint skeletal connective tissues in rats.

Materials and methods. We performed a morphometric evaluation of articular cartilages (their thickness, extracellular matrix arrangement, spatial arrangement of the main components, distribution density, and main cellular indices of chondrocytes), as well as changes in subchondral bones (the presence of trabeculae in the basal layer of the articular cartilage and individual osteophytes) in 30 rats with a model of primary osteoarthrosis induced by sequential administration of 0.5 ml dexamethasone (2 mg) and 1 ml 10% sterile talc suspension mixed with normal saline into the joint cavity. We studied the histologic specimens of the knee joints stained with hematoxylin – eosin, Alcian blue (рН 1.0 and 2.5), as well as with Van Gieson’s, Masson’s, and Mallory’s trichome stains. The metabolic features of the articular cartilage and bone tissues were investigated by determining the hyaluronan, osteocalcin, and type I collagen levels in the serum of the rats.

Results. In the rats with dexamethasone- and talc-induced osteoarthrosis, the thickness of cartilages in their weight-bearing areas decreased by 50%, the spatial arrangement of chondrocytes was impaired, and the nuclear – cytoplasmatic ratio (р < 0.01) decreased to 0.3. Besides, a rise in the serum levels of hyaluronan (p < 0.001) to 110.2 ng / ml, type I collagen fragments (p < 0.001) to 217.9 ng / ml, and osteocalcin (p < 0.001) to 231.1 ng / ml was detected.

Conclusion. The main pathogenetic features of experimental osteoarthrosis induced by dexamethasone and talc include impaired distribution density, morphological characteristics, and functional activity of chondrocytes, which results in inhibited synthesis of extracellular matrix components in the articular cartilage and activated destruction of proteoglycans containing unsulphated glycosaminoglycans. The subchondral bone remodeling in experimental osteoarthrosis induced by dexamethasone and talc is characterized by intensification of synthetic activity of osteoblasts.

1. Лапшина С.А., Мухина Р.Г., Мясоутова Л.И. Остеоартроз: современные проблемы терапии. Русский медицинский журнал. 2016;24(2):95–101.

2. Щелкунова Е.И., Воропаева А.А., Русова Т.В., Штопис И.С. Применение экспериментального моделирования при изучении патогенеза остеоартроза (обзор литературы). Сибирский научный медицинский журнал. 2019;39(2):27–39. DOI: 10.15372/SSMJ20190203.

3. Алексеева Л.И. Новые представления о патогенезе остеоартрита, роль метаболических нарушений. Ожирение и метаболизм. 2019;16(2):75–82. DOI: 10.14341/omet10274

4. Патент РФ № 95106870, М. кл. G 09 B 23/28 1997.

5. Kuyinu E.L., Narayanan G., Nair L.S., Laurencin C.T. Animal models of osteoarthritis: classification, update, and measurement of outcomes. Journal of Orthopaedic Surgery and Research. 2016;(11):19. DOI: 10.1186/s13018-016-0346-5.

6. Mazor M., Best T.M., Cesaro A., Lespessailles E., Toumi H. Osteoarthritis biomarker responses and cartilage adaptation to exercise: A review of animal and human models. Scand. J. Med. Sci. Sports. 2019;29(8):1072–1082. DOI: 10.1111/sms.13435.

7. Cope P.J., Ourradi K., Li Y., Sharif M. Models of osteoarthritis: the good, the bad and the promising. Osteoarthritis and Cartilage. 2019;27(2):230–239. DOI: 10.1016/j.joca.2018.09.016.

8. Новочадов В.В., Крылов П.А., Зайцев В.Г. Неоднородность строения гиалинового хряща коленного сустава у интактных крыс и при экспериментальном остеоартрозе. Вестник Волгоградского государственного университета. Сер. 11: Естественные науки. 2014;(4):7–16. DOI: 10.15688/jvolsu11.2014.4.1.

9. Lu Z., Luo M., Huang Y. IncRNA‐CIR regulates cell apoptosis of chondrocytesin osteoarthritis. J. Cell Biochem. 2018;(120):7229–7237. DOI: 10.1002/jcb.27997.

10. Uthman I., Raynauld J.-P., Haraoui B. Intra-articular therapy in osteoarthritis. Postgrad. Med. J. 2003;(79):449–453. DOI: 10.1136/pmj.79.934.449.

11. Szychlinska M.A., Leonardi R., Al-Qahtani M., Mobasheri A., Musumeci G. Altered joint tribology in osteoarthritis: Reduced lubricin synthesis due to the inflammatory process. New horizons for therapeutic approaches. Annals of Physical and Rehabilitation Medicine. 2016;59(3):149–156. DOI: 10.1016/j.rehab.2016.03.005.

12. Glasson S.S., Chambers M.G., van Den Berg W.B., Little C.B. The OARSI histopathology initiative recommendations for histological assessments of osteoarthritis in the mouse. Osteoarthritis and Cartilage. 2010;(18):17–23. DOI: 10.1016/j.joca.2010.05.025.

13. Карякина Е.В., Гладкова Е.В., Пучиньян Д.М. Структурно-метаболические особенности суставных тканей в условиях дегенеративной деструкции и ревматоидного воспаления. Российский физиологический журнал им. И.М. Сеченова. 2019;105(8):989–1001. DOI: 10.1134/s0869813919080065.

14. MacKay J.W., Murray P.J., Kasmai B., Johnson G., Donell S.T., Toms A.P. Subchondral bone in osteoarthritis: association between MRI texture analysis and histomorphometry. Osteoarthritis and Cartilage. 2017;25(5):700–707. DOI: 10.1016/j.joca.2016.12.011.

15. Ashraf S., Mapp P.I., Walsh D.A. Contributions of angiogenesis to inflammation, joint damage, and pain in a rat model of osteoarthritis. Arthritis & Rheumatism. 2011;63(9):2700– 2710. DOI: 10.1002/art.30422.