Sains Malaysiana 51(11)(2022): 3741-3754

http://doi.org/10.17576/jsm-2022-5111-18

Changes of Grip Strength, Articular Cartilage and Subchondral Bone in Monoiodoacetate-Induced Osteoarthritis in Rats

(Perubahan pada Kekuatan Genggaman, Rawan Artikul dan Tulang Subkondral dalam Osteoartritis Aruhan Monoiodoasetat pada Tikus)

SOPHIA OGECHI EKEUKU¹, FAIRUS AHMAD² & KOK-YONG CHIN^1,*

¹Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Federal Territory, Malaysia

²Department of Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Federal Territory, Malaysia

Received: 24 August 2021/Accepted: 27 June 2022

Abstract

Osteoarthritis is a degenerative disease affecting articular cartilage among the elderly. The intra-articular monoiodoacetate injection is one of the most widely used methods to induce osteoarthritis in animals. While the effects of monoiodoacetate on cartilage are well-characterized, its effects on subchondral bone remodeling are less studied. The purpose of this study was to determine the changes of the grip strength, articular cartilage structure and subchondral bone remodeling in monoiodoacetate-induced osteoarthritis in rats. Three-month-old male Wistar rats were assigned to normal control (n=6) and osteoarthritis group (n=6), which received intra-articular injection of 4 mg/50 µL monoiodoacetate solution once at the left knee of hindlimb. The rats were monitored for four weeks. The grip strength test was performed before injection and every week after injection. After four weeks, the femurs with intact cartilage were harvested for histomorphological analysis. Grip strength was reduced significantly in the osteoarthritic rats compared to the normal rats (p<0.05). Food intake was reduced significantly one week following monoiodoacetate-induction (p<0.05), but it stabilized afterwards. Monoiodoacetate injection increased cartilage erosion and osteoclast number in the subchondral bone of the osteoarthritic rats compared to the normal rats (p<0.05). However, it did not affect body weight, subchondral bone osteoblast activity, mineralization and microstructure of osteoarthritic rats (p>0.05). As a conclusion, monoiodoacetate-induced osteoarthritis affects the cartilage and increases osteoclast formation in the subchondral bone of rats.

Keywords: Femur; monoiodoacetate; osteoarthritis; subchondral bone

Abstrak

Osteoartritis ialah penyakit degeneratif yang merosakkan rawan artikul dalam kalangan warga tua. Suntikan intra-artikul monoiodoasetat merupakan salah satu kaedah yang paling biasa digunakan untuk mengaruh osteoartritis pada haiwan. Walaupun kesan monoiodoasetat ke atas rawan telah diperincikan, kesannya terhadap penukargantian tulang subkondral kurang dikaji. Tujuan kajian ini adalah untuk menentukan perubahan kekuatan genggaman, struktur rawan artikul dan penukargantian tulang subkondral dalam osteoartritis aruhan monoiodoasetat pada tikus. Tikus Wistar berumur tiga bulan telah dibahagi kepada kumpulan kawalan normal (n=6) dan osteoartritis (n=6) yang menerima suntikan intra-artikul larutan monoiodoasetat pada 4 mg/50 µL sekali pada sendi kiri kaki belakang. Tikus tersebut telah diperhatikan selama empat minggu. Ujian kekuatan genggaman telah dilakukan sebelum suntikan dan setiap minggu selepas suntikan. Selepas empat minggu, femur dengan rawan yang tidak diaruh telah diambil untuk analisis histomorfometri. Kekuatan genggaman telah menurun secara signifikan pada tikus yang mempunyai osteoartritis berbanding dengan tikus normal (p<0.05). Pengambilan makanan telah berkurang secara signifikan satu minggu selepas aruhan monoiodoasetat (p<0.05), tetapi ia menjadi stabil selepas itu. Suntikan monoiodoasetat telah meningkatkan hakisan rawan dan bilangan osteoklas dalam tulang subkondral pada tikus yang mempunyai osteoartritis berbanding dengan tikus normal (p<0.05). Walau bagaimanapun, ia tidak mengganggu berat badan, aktiviti osteoblas, mineralisasi dan mikrostruktur pada tulang subkondral tikus osteoartritis (p>0.05). Secara kesimpulannya, osteoartritis aruhan monoiodoasetat memberi kesan terhadap rawan dan meningkatkan pembentukan osteoklas dalam tulang subkondral tikus.

Kata kunci: Femur; monoiodoasetat; osteoartritis; tulang subkondral

References

Al-Saadi, H.M., Chin, K.Y., Ahmad, F., Mohd Ramli, E.S., Arlamsyah, A.M., Japar Sidik, F.Z., Abdul Hamid, J. & Soelaiman, I.N. 2021. Effects of palm tocotrienol-rich fraction alone or in combination with glucosamine sulphate on grip strength, cartilage structure and joint remodelling markers in a rat model of osteoarthritis. Applied Sciences  11: 18. https://doi.org/10.3390/app11188577

Asjid, R., Faisal, T., Qamar, K., Malik, S., Umbreen, F. & Fatima, M. 2019. Effect of platelet-rich plasma on mankin scoring in chemically-induced animal model of osteoarthritis. Journal of the College of Physicians and Surgeons Pakistan 29(11): 1067-1071. https://doi.org/10.29271/jcpsp.2019.11.1067

Ayhan, E., Kesmezacar, H. & Akgun, I. 2014. Intraarticular injections (corticosteroid, hyaluronic acid, platelet rich plasma) for the knee osteoarthritis. World Journal of Orthopedics 5(3): 351-361. https://doi.org/10.5312/wjo.v5.i3.351

Bagi, C.M., Berryman, E., Zakur, D.E., Wilkie, D. & Andresen, C.J. 2015. Effect of antiresorptive and anabolic bone therapy on development of osteoarthritis in a posttraumatic rat model of OA. Arthritis Research & Therapy 17(1): 315. https://doi.org/10.1186/s13075-015-0829-5

Burr, D.B. & Gallant, M.A. 2012. Bone remodelling in osteoarthritis. Nature Reviews Rheumatology 8(11): 665-673. https://doi.org/10.1038/nrrheum.2012.130

Chin, K.Y., Wong, S.K., Sidik, F.Z.J., Hamid, J.A., Abas, N.H., Ramli, E.S.M., Mokhtar, S.A., Rajalingham, S. & Nirwana, S.I. 2019. The effects of annatto tocotrienol supplementation on cartilage and subchondral bone in an animal model of osteoarthritis induced by monosodium iodoacetate. International Journal of Environmental Research and Public Health 16(16): 2897. https://doi.org/10.3390/ijerph16162897

Cobos, E. & Portillo-Salido, E. 2013. “Bedside-to-Bench” behavioral outcomes in animal models of pain: Beyond the evaluation of reflexes. Current Neuropharmacology 11(6): 560-591. https://doi.org/10.2174/1570159x113119990041

Deacon, R.M.J. 2013. Measuring the strength of mice. Journal of Visualized Experiments 76: 2610. https://doi.org/10.3791/2610

Dulay, G.S., Cooper, C. & Dennison, E.M. 2015. Knee pain, knee injury, knee osteoarthritis & work. Best Practice and Research: Clinical Rheumatology 29(3): 454-461. https://doi.org/10.1016/j.berh.2015.05.005

Gallo, J., Raska, M., Kriegova, E. & Goodman, S.B. 2017. Inflammation and its resolution and the musculoskeletal system. Journal of Orthopaedic Translation 10: 52-67. https://doi.org/10.1016/j.jot.2017.05.007

Guzman, R.E., Evans, M.G., Bove, S., Morenko, B. & Kilgore, K. 2003. Mono-Iodoacetate-induced histologic changes in subchondral bone and articular cartilage of rat femorotibial joints: AN animal model of osteoarthritis. Toxicologic Pathology 31(6): 619-624. https://doi.org/10.1080/01926230390241800

Henrotin, Y., Pesesse, L. & Sanchez, C. 2012. Subchondral bone and osteoarthritis: Biological and cellular aspects. Osteoporosis International 23(8 SUPPL): S847-51. https://doi.org/10.1007/s00198-012-2162-z

Henson, F.M.D. & Vincent, T.A. 2008. Alterations in the vimentin cytoskeleton in response to single impact load in an in vitro model of cartilage damage in the rat. BMC Musculoskeletal Disorders 9(1): 94. https://doi.org/10.1186/1471-2474-9-94

Hügle, T. & Geurts, J. 2016. What drives osteoarthritis? - synovial versus subchondral bone pathology. Rheumatology (Oxford) 56(9): 1461-1471. https://doi.org/10.1093/rheumatology/kew389

Hunter, D.J. 2011. Pharmacologic therapy for osteoarthritis-the era of disease modification. Nature Reviews Rheumatology 7(1): 13-22. https://doi.org/10.1038/nrrheum.2010.178

Ji, B., Zhang, Z., Guo, W., Ma, H., Xu, B., Mu, W., Amat, A. & Cao, L. 2018. Isoliquiritigenin blunts osteoarthritis by inhibition of bone resorption and angiogenesis in subchondral bone. Scientific Reports 8(1): 1721. https://doi.org/10.1038/s41598-018-19162-y

Kulak, C.A.M. & Dempster, D.W. 2010. Bone histomorphometry: A concise review for endocrinologists and clinicians. Arquivos Brasileiros de Endocrinologia & Metabologia 54(2): 87-98. https://doi.org/10.1590/S0004-27302010000200002

Lampropoulou-Adamidou, K., Lelovas, P., Karadimas, E.V., Liakou, C., Triantafillopoulos, I.K., Dontas, I. & Papaioannou, N.A. 2014. Useful animal models for the research of osteoarthritis. European Journal of Orthopaedic Surgery and Traumatology 24(3): 263-271. https://doi.org/10.1007/s00590-013-1205-2

Li, G., Yin, J., Gao, J., Cheng, T.S., Pavlos, N.J., Zhang, C. & Zheng, M.H. 2013. Subchondral bone in osteoarthritis: Insight into risk factors and microstructural changes. Arthritis Research and Therapy 15(6): 223. https://doi.org/10.1186/ar4405

Litwic, A., Edwards, M.H., Dennison, E.M. & Cooper, C. 2013. Epidemiology and burden of osteoarthritis. British Medical Bulletin 105: 185-199. https://doi.org/10.1093/bmb/lds038

McErlain, D.D., Ulici, V., Darling, M., Gati, J.S., Pitelka, V., Beier, F. & Holdsworth, D.W. 2012. An in vivo investigation of the initiation and progression of subchondral cysts in a rodent model of secondary osteoarthritis. Arthritis Research and Therapy 14(1): R26-R26. https://doi.org/10.1186/ar3727

Murat, N., Karadam, B., Ozkal, S., Karatosun, V. & Gidener, S. 2007. Quantification of papain-induced rat osteoarthritis in relation to time with the Mankin score. Acta Orthopaedica Et Traumatologica Turcica 41(3): 233-237.

Namhong, S., Wongdee, K., Suntornsaratoon, P., Teerapornpuntakit, J., Hemstapat, R. & Charoenphandhu, N. 2020. Knee osteoarthritis in young growing rats is associated with widespread osteopenia and impaired bone mineralization. Scientific Reports 10(1): 15079. https://doi.org/10.1038/s41598-020-71941-8

Network, G.B. of D. C. 2020. Global Burden of Disease Study 2019 (GBD 2019) results. Osteoarthritis —level 3 cause. http://www.healthdata.org/results/gbd_summaries/2019/osteoarthritis-level-3-cause.

Otis, C., Guillot, M., Moreau, M., Martel-Pelletier, J., Pelletier, J.P., Beaudry, F. & Troncy, E. 2017. Spinal neuropeptide modulation, functional assessment and cartilage lesions in a monosodium iodoacetate rat model of osteoarthritis. Neuropeptides 65: 56-62. https://doi.org/10.1016/j.npep.2017.04.009

Pitcher, T., Sousa-Valente, J. & Malcangio, M. 2016. The monoiodoacetate model of osteoarthritis pain in the mouse. Journal of Visualized Experiments 2016(111): 53746. https://doi.org/10.3791/53746

Robinson, W.H., Lepus, C.M., Wang, Q., Raghu, H., Mao, R., Lindstrom, T.M. & Sokolove, J. 2016. Low-grade inflammation as a key mediator of the pathogenesis of osteoarthritis. Nature Reviews Rheumatology 12(10): 580-592. https://doi.org/10.1038/nrrheum.2016.136

Salo, P.T., Hogervorst, T., Seerattan, R.A., Rucker, D. & Bray, R.C. 2002. Selective joint denervation promotes knee osteoarthritis in the aging rat. Journal of Orthopaedic Research 20(6): 1256-1264. https://doi.org/10.1016/S0736-0266(02)00045-1

Samvelyan, H.J., Hughes, D., Stevens, C. & Staines, K.A. 2021. Models of osteoarthritis: Relevance and new insights. Calcified Tissue International 109(3): 243-256. https://doi.org/10.1007/s00223-020-00670-x

Sharma, V., Anuvat, K., John, L. & Davis, M. 2017. Scientific American pain management-arthritis of the knee. Decker: Pain Related Disease States.

Sinusas, K. 2012. Osteoarthritis: Diagnosis and treatment. American Family Physician 85(1): 49-56.

Steinmeyer, J., Bock, F., Stöve, J., Jerosch, J. & Flechtenmacher, J. 2018. Pharmacological treatment of knee osteoarthritis: Special considerations of the new German guideline. Orthopedic Reviews 10(4): 7782. https://doi.org/10.4081/or.2018.7782

Sur, D. & Chakravorty, R. 2016. Relationship of thyroid and sex hormones with osteoarthritis in postmenopausal Indian women. Journal of Clinical Gynecology and Obstetrics 5(4): 117-120. https://doi.org/10.14740/jcgo410e

Suri, S. & Walsh, D.A. 2012. Osteochondral alterations in osteoarthritis. Bone 51(2): 204-211. https://doi.org/10.1016/j.bone.2011.10.010

Yang, Y., Li, P., Zhu, S. & Bi, R. 2020. Comparison of early-stage changes of osteoarthritis in cartilage and subchondral bone between two different rat models. PeerJ 2020(4): e8934-e8934. https://doi.org/10.7717/peerj.8934

Zhang, L., Hu, H., Tian, F., Song, H. & Zhang, Y. 2011. Enhancement of subchondral bone quality by alendronate administration for the reduction of cartilage degeneration in the early phase of experimental osteoarthritis. Clinical and Experimental Medicine 11(4): 235-243. https://doi.org/10.1007/s10238-011-0131-z

^*Corresponding author; email: chinkokyong@ppukm.ukm.edu.my