Morphological changes in the tissues of the knee joints of rats in carrageenan-induced experimental arthritis

  • O. V. Pelypenko Ukrainian Medical Stomatological Academy, Poltava, Ukraine
Keywords: osteoarthritis, knee joint, rats, carrageenan.


Every fifth inhabitant of the earth has been diagnosed with osteoarthritis of various etiologies. Morphological studies of arthritis provide a theoretical basis for creating optimal treatments for this pathology. Given the polyetiological nature of the disease, the choice of the optimal experimental model, which would be as close as possible to the real conditions of inflammatory process reproduction, is the topical issue. The purpose of the study was to confirm the pathological reaction of the joint tissues of laboratory animals in response to intraperitoneal administration of ƛ-carrageenan. The study was performed on 50 white Wistar rats males aged 12 weeks, weighing 130-150 g. The animals were euthanized by an overdose of anaesthesia according to the terms of the study (1 - 30 days). Fragments of the distal metaepiphyses of the femur and proximal metaepiphyses of the tibia were used for histological examination. Staining of sections obtained on the microtome was performed with haematoxylin, eosin, and Van Gieson`s stain. From the first day of the experimental study, a corresponding reaction of the joint tissues was being observed. Particularly pronounced were the changes in the synovial membrane in the form of oedema of the villi accompanied by an increased filling of blood vessels with foci of thrombosis. Gradually, up to 5 days in the synovial membrane, proliferative changes took place with a clear definition of the multilineage of the integumentary layer, vascular reaction with a tendency to thrombosis, in some places necrosis of synoviocytes was observed, but relative integrity of the morphological structure was still provided by protective barriers of bone and cartilage. On the 7th day pronounced resorption of both bone and cartilage tissue occurred, tissue structure became disorganized and functional layer became thin, accompanied by massive intracellular lysis. The process of synoviocytes necrobiosis with fatty degeneration spread. The histological picture of 10 days is characterized by generalized destruction of bone beams; the destroyed cartilage was replaced by granulation tissue with the presence of cavities. Massive foci of lymphocytic infiltration were observed in the synovial membrane. On the 14th day, a fragmentation of cartilage happened, most of the bone beams (trabeculae) were destroyed. After 3 weeks the morphological picture of cartilage tissue was determined by the appearance in the lacunae of viable cells, the number of which was close to normal. Bone beams were restored, although they remained thin. In a synovial membrane, the hyperplasia of apical departments of villi, leukocytes infiltration, disorganization of connective tissue, and separate vascular disturbances remained. 30 days of the experiment were characterized by a relative recovery of structural relationships to normal. The obtained data confirm the feasibility of using carrageenan in experimental studies of osteoarthritis.


[1] Alekseeva, L. I., Taskina, E. A., & Kashevarova, N. G. (2019). Osteoarthritis: epidemiology, classification, risk factors, and progression, clinical presentation, diagnosis, and treatment. Modern Rheumatology Journal, 13(2), 9-21. doi: 10.14412/1996-7012-2019-2-9-21
[2] Bailey, K. N., Furman, B. D., Zeitlin, J., Kimmerling, K. A., Wu, C. L., Guilak, F., & Olson S. A. (2020). Intra-articular depletion of macrophages increases acute synovitis and alters macrophage polarity in the injured mouse knee. Osteoarthritis and cartilage, 28(5), 626-638. doi: 10.1016/j.joca.2020.01.015
[3] Bittencourt, J. A., Neto, M. F., Lacerda, P. S., Bittencourt, R. C., Silva, R. C., Lobato, C. C., … Santos, C. B. (2019). In Silico Evaluation of Ibuprofen and Two Benzoylpropionic Acid Derivatives with Potential Anti-Inflammatory Activity. Molecules, 24(8), 1476. doi: 10.3390/molecules24081476
[4] Buch, M. H, Eyre, S., & McGonagle D. (2021). Persistent inflammatory and non-inflammatory mechanisms in refractory rheumatoid arthritis. Nat Rev Rheumatol, 17(1), 17-33. doi: 10.1038/s41584-020-00541-7
[5] Cordeiro, M. S., Simas, D. L., Pérez-Sabino, J. F., Mérida-Reyes, M. S., Muñoz-Wug, M. A., Oliva-Hernández, B. E., ... Giorno, T. (2020). Characterization of the Antinociceptive Activity from Stevia serrata. Cav. Biomedicines, 8(4), 79. doi: 10.3390/biomedicines8040079
[6] Delco, M. L., Kennedy, J. G., Bonassar, L. J., & Fortier, L. A. (2017). Post-traumatic osteoarthritis of the ankle: A distinct clinical entity requiring new research approaches. J Orthop Res, 35(3), 440-453. doi: 10.1002/jor.23462
[7] Gaynetdinova, A. N., Zalyalyutdinova, L. N., Abdulganieva, D. I., Imanaeva, A. Ya., & Gayfullin, A. N. (2015). Экспериментальное обоснование применения тиоктовой кислоты с метотрексатом в комбинированной терапии ревматоидного артрита на модели адъювантного артрита [Experimental basis of thioctic acid addicton to methotrexate in combined therapy of rheumatoid arthritis by adjuvant arthritis model]. Инновационные технологии в медицине – Innovative technologies in medicine, 4(89), 19-23.
[8] Golovach, I. Y., & Yehudina, Y. D. (2019). Posttraumatic osteoarthritis: contemporary views of development, progression and therapeutic approaches. Политравма – Polytrauma, (1), 82-89.
[9] Gromyko, M. V., & Gritsuk A. I. (2012). Экспериментальные модели ревматоидного артрита [Experimental models of rheumatoid arthritis]. Проблемы здоровья и экологии – Health and Ecology Issues, 2(32), 115-118.
[10] Henriques, M. G., Silva, P. M., Martins, M. A., Flores, C. A., Cunha, F. Q., Assreuy-Filho, J., & Cordeiro, R. S. (1987). Mouse paw oedema. A new model for inflammation?. Braz. J. Med. Biol. Res., 20(2), 243-249. PMID: 3690058
[11] Hladkykh, F. V., Student, V. O., Stepaniuk, N. H., & Vernyhorodskyi, S. V. (2017). Патоморфологическое и компьютерное томографическое исследование влияния ибупрофена и его комбинации с 2-фенил-3-карбетокси-4-диметиламино-метил-5-оксибензофурана гидрохлоридом (винбороном) на состояние суставов нижних конечностей крыс с экспериментальным ревматоидным артритом [Pathomorphological and computerized tomography study of ibuprofen and combination with 2-phenyl-3-carbethoxy-4-dimethylaminomethyl-5-oksibenzofuran hydrochloride (vinboron) influence on the joints of lower extremities of rats with experimental rheumatoid arthritis]. Фармация и фармакология – Pharmacy & Pharmacology, 5(5), 457-486. doi: 10.19163/2307-9266-2017-5-5-457-486
[12] Kuyinu, E. L., Narayanan, G., Nair, L. S., & Laurencin, C. T. (2016). Animal models of osteoarthritis: classification, update, and measurement of outcomes. J Orthopaedic Surg Res, (11), 19. doi: 10.1186/s13018-016-0346-5
[13] Levy, L. (1969). Carrageenan paw edema in the mouse. Life Sci, 8(11), 601-606. doi: 10.1016/0024-3205(69)90021-6
[14] McCoy, A. M. (2015). Animal Models of Osteoarthritis: Comparisons and Key Considerations. Vet. Pathol, 52(5), 803-818. doi: 10.1177/0300985815588611
[15] Muzhikyan, A. A., Shekunova, E. V., Kashkin, V. A., Makarova, M. N., & Makarov, V. G. (2018). Histological evaluation of joint pathology in various models of chronic arthritis in rats. Laboratory Animals for Science, 1, 32-45. doi: 10.29926/2618723X-2018-01-04
[16] Nasonov, E. L. (2017). Фармакотерапия ревматоидного артрита: новая стратегия, новые мишени [Pharmacotherapy for rheumatoid arthritis: new strategy, new targets]. Научно-практическая ревматология – Rheumatology Science and Practice, 55(4), 409-419. doi: 10.14412/1995-4484-2017-409-419
[17] Nosivets, D. S. (2019). Экспериментальные модели патологии хрящевой ткани [Experimental models of cartilage tissue pathology]. Запорожский медицинский журнал – Zaporozhye medical journal, 21(4), 554-560. doi: 10.14739/2310-1210.2019.4.173362.
[18] Pelypenko, A. V., Shepitko, V. I., & Pelypenko, L. B. (2019). Morphofunctional characteristics of a microcirculatory beds subchondral bone at the introduction of cryo-conversed placenta on the background of aseptic inflammation in the rat. World of medicine and biology, 2(68), 187-191. doi: 10.26724/2079-8334-2019-2-68-187-191
[19] Ponyk, R. M., & Korytko, Z. I. (2019). Захворюваність та особливості реабілітації хворих на ревматоїдний артрит в умовах сьогодення [Disease and peculiarities of rehabilitation of patients with rheumatoid arthritis in the present time]. Здобутки клінічної і експериментальної медицини – Achievements of Clinical and Experimental Medicine, (3), 183-187. doi: 10.11603/1811-2471.2019.v.i3.10504
[20] Posadas, I., Bucci, M., Roviezzo, F., Rossi, A., Parente, L., Sautebin, L., & Cirino, G. (2004). Carrageenan induced mouse paw oedema is biphasic, age weight dependent and displays differential nitric oxide cyclooxygenase 2 expression. British Journal of Pharmacology, 142(2), 331-338. doi: 10.1038/sj.bjp.0705650
[21] Punzi, L., Galozzi, P., Luisetto, R., Favero, M., Ramonda, R., Oliviero, F., & Scanu, A. (2016). Post-traumatic arthritis: overview on pathogenic mechanisms and role of inflammation. RMD Open, 2(2), e000279. doi: 10.1136/rmdopen-2016-000279
[22] Shepitko, V. I., & Pelypenko, O. V. (2015). Cучасні погляди на структурну організацію суглобових тканин [Current concepts of the structural organization of joint tissues]. Світ медицини та біології – World of medicine and biology, 3(52), 175-183.
[23] Sugishita, E., Amagaya, S., & Ogihara, Y. (1981). Anti-inflammatory testing methods: comparative evaluation of mice and rats. J. Pharmacobiodyn, 4(8), 565-575. doi: 10.1248/bpb1978.4.565
How to Cite
Pelypenko , O. V. (2021). Morphological changes in the tissues of the knee joints of rats in carrageenan-induced experimental arthritis. Biomedical and Biosocial Anthropology, (40), 12-17.