Background: The aim was to investigate the time- and dose-related changes in the behavioral and pathological characteristics in the MIA-induced KOA model rat.
Methods: MIA (40, 50, and 60 mg/mL) was injected into the left joint of male Sprague–Dawley rats. After 2 weeks, the changes in the KOA rat model were observed by behavioral evaluation, imaging-level evaluation, and histological-level evaluation. The changes were also compared after 40-mg/mL MIA injection for 2 and 6 weeks.
Results: MIA-induced bone surface defects, osteophyte hyperplasia around the articular rim, increased subchondral bone density, thinning of the sparse trabecular bone, structural disorder, and local clustering were observed. The degree of injury gradually increased with the increase in MIA concentration. After 6 weeks, subchondral bone density and sparse trabecular bone increased in the KOA model.
Conclusions: The severity of the model also increased significantly with the changes in dose and time. In dose-dependent experiments, this study revealed that 40 mg/mL was the optimal dose to induce significant pathological changes without causing undue discomfort or death in animals. This dose may induce pathological changes stably and is suitable for long-term observation.
| [1] |
Brophy RH, Fillingham YA. AAOS clinical practice guideline summary: management of osteoarthritis of the knee (nonarthroplasty). J Am Acad Orthop Surg. 2022; 30(9): e721-e729.
|
| [2] |
Wang S, Lin Y, Tao S. Analysis of influential factors of knee osteoarthritis in middle-aged and old people. Chin Med Herald. 2021; 18(27): 80-83.
|
| [3] |
GBD 2021 Osteoarthritis Collaborators. Global, regional, and national burden of osteoarthritis, 1990–2020 and projections to 2050: a systematic analysis for the Global Burden of Disease Study 2021. Lancet Rheumatol. 2023; 5(9): e508-e522.
|
| [4] |
Tan X, Guo Y. Research progress on predisposing factors of knee osteoarthritis. Rheum Arthritis. 2022; 11(1): 60-64.
|
| [5] |
Kolasinski SL, Neogi H, Hochberg MC, et al. American College of Rheumatology/Arthritis Foundation guideline for the management of osteoarthritis of the hand, hip, and knee. Arthritis Care Res. 2020; 72(2): 149-162.
|
| [6] |
Joint Surgery Group, Society of Osteology, Chinese Medical Association. Osteoarthritis treatment guide (2018 edition). Chin J Orthop. 2018; 38(12): 705-715.
|
| [7] |
Joint Surgery Group, Society of Osteology, Chinese Medical Association, et al. Chinese guideline for diagnosis and treatment of osteoarthritis (2021 edition). Chin J Orthop. 2021; 41(18): 1291-1314.
|
| [8] |
Xie Y. Effect of non-steroidal anti-inflammatory drugs on gastrointestinal function in elderly users. Clin Med. 2021; 41(8): 87-89.
|
| [9] |
Cooper C, Chapurlat R, Al-Daghri N, et al. Safety of oral non-selective non-steroidal antiinflammatory drugs in osteoarthritis:what does the literature say. Drugs Aging. 2019; 36(1): 15-24.
|
| [10] |
Otis C, Guillot M, Moreau M, et al. Spinal neuropeptide modulation, functional assessment and cartilage lesions in a monosodium iodoacetate rat model of osteoarthritis. Neuropeptides. 2017; 65: 56-62.
|
| [11] |
Bao Z, Chen M, Li C, Shan Q, Wang Y, Yang W. Monosodium iodoacetate- induced subchondral bone microstructure and inflammatory changes in an animal model of osteoarthritis. Open Life Sci. 2022; 17(1): 781-793.
|
| [12] |
van Osch GJ, van der Kraan PM, van den Berg WB. Site-specific cartilage changes in murine degenerative knee joint disease induced by iodoacetate and collagenase. J Orthop Res. 1994; 12(2): 168-175.
|
| [13] |
Dumond H, Presle N, Pottie P, et al. Site specific changes in gene expression and cartilage metabolism during early experimental osteoarthritis. Osteoarthr Cartil. 2004; 12(4): 284-295.
|
| [14] |
Takahashi I, Matsuzaki T, Kuroki H, Hoso M. Induction of osteoarthritis by injecting monosodium iodoacetate into the patellofemoral joint of an experimental rat model. PLoS One. 2018; 13(4):e0196625.
|
| [15] |
Morais SV, Czeczko NG, Malafaia O, et al. Osteoarthritis model induced by intra-articular monosodium iodoacetate in rats knee. Acta Cir Bras. 2016; 31(11): 765-773.
|
| [16] |
Jiang C, Wang Z, Li J. Analysis on mechanism of Huangwu Ganfu ointment in relieving knee osteoarthritis pain based on network pharmacology and Expewimental verification. Inf J Chin Med. 2024; 31(1): 20-28.
|
| [17] |
Kwon M, Nam D, Kim J. Pathological characteristics of monosodium iodoacetate-induced osteoarthritis in rats. Tissue Eng Regen Med. 2023; 20(3): 435-446.
|
| [18] |
Wang T, Mao D, Huang Y. Effects of stellate ganglion block on pain behavior of rats with central pain after spinal cord injury and its mechanism. J Guizhou Med Univ. 2023; 48(11): 1350-1356.
|
| [19] |
Lu J, Wei H, Xu X. Schisandra Balleviates inflammatory response and DA neurons in PD mice by inhibiting TLR4/NF-κB signaling pathway. Chin J Immunol. 2022; 38(4): 427-431.
|
| [20] |
Li Y, Fan H, Chai Z. Neuroprotective and anti-inflammatory effects of Wuzi Yanzong pills on Parkinson's disease mice. Chin J Tradit Chin Med. 2020; 35(7): 3623-3626.
|
| [21] |
Khodir SA, Al-Gholam MA, Salem HR. L-carnitine potentiates the anti-inflammatory and antinociceptive effects of diclofenac sodium in an experimentally-induced knee osteoarthritis rat model. Iran J Basic Med Sci. 2020; 23(8): 1035-1044.
|
| [22] |
Zarringam D, Saris DBF, Bekkers JEJ. The value of SPECT/CT for knee osteoarthritis: a systematic review. Cartilage. 2021; 12(4): 431-437.
|
| [23] |
Culvenor AG, Ruhdorfer A, Juhl C, Eckstein F, Øiestad BE. Knee extensor strength and risk of structural, symptomatic, and functional decline in knee osteoarthritis: a systematic review and meta-analysis. Arthritis Care Res. 2017; 69(5): 649-658.
|
| [24] |
Li P, Lin J, Wang G. Research progress on knee osteoarthritis in traditional Chinese and Western medicine. World Tradit Chin Med. 2022; 17(16): 2373-2377.
|
| [25] |
McCoy AM. Animal models of osteoarthritis: comparisons and key considerations. Vet Pathol. 2015; 52(5): 803-818.
|
| [26] |
Wang M, Ju S, Liu P. A comparative study on the rat models of knee osteoarthritis induced by Papain,Sodium lodoacetate and type II collagenase. Sichuan Yi Xue. 2020; 41(2): 126-131.
|
| [27] |
Wang FS, Kuo CW, Ko JY, et al. Irisin mitigates oxidative stress, chondrocyte dysfunction and osteoarthritis development through regulating mitochondrial integrity and autophagy. Antioxidants. 2020; 9(9):810.
|
| [28] |
Mobasheri A, Bondy CA, Moley K, et al. Facilitative glucose transporters in articular chondrocytes. Expression, distribution and functional regulation of GLUT isoforms by hypoxia, hypoxia mimetics, growth factors and pro-inflammatory cytokines. Adv Anat Embryol Cell Biol. 2008; 200: 1-84.
|
| [29] |
Milaras C, Lepetsos P, Dafou D, Potoupnis M, Tsiridis E. Association of Matrix Metalloproteinase (MMP) gene polymorphisms with knee osteoarthritis: a review of the literature. Cureus. 2021; 13(10):e18607.
|
| [30] |
Singh S, Jindal D, Khanna R. Can serum MMP-3 diagnose early knee osteoarthritis? J Orthop Translat. 2023; 38: 42-46.
|
| [31] |
Koelling S, Clauditz TS, Kaste M, Miosge N. Cartilage oligomeric matrix protein is involved in human limb development and in the pathogenesis of osteoarthritis. Arthritis Res Ther. 2006; 8(3): R56.
|
| [32] |
Cui J, Zhang J. Cartilage oligomeric matrix protein, diseases, and therapeutic opportunities. Int J Mol Sci. 2022; 23(16): 9253.
|
| [33] |
Shi H, Tang Z, Guo M, et al. Exploration of methodology and role of sodium iodoacetate in modeling of rat osteoarthritis. Chin J Joint Surg. 2023; 17(4): 534-539.
|
| [34] |
Schuelert N, McDougall JJ. Grading of monosodium iodoacetate-induced osteoarthritis reveals a concentration-dependent sensitization of nociceptors in the knee joint of the rat. Neurosci Lett. 2009; 465(2): 184-188.
|
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