Abstract
Background: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPS) play a key role in the pathogenesis of osteoarthritis (OA). Recent research showed the involvement of some MMPs in COVID-19, but the results are limited and contradictory.
Objective: In this study, we investigated the levels of MMPs (MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10) and TIMP-1 in the plasma of patients with OA after recovery from COVID- 19.
Methods: The experiment involved patients aged 39 to 80 diagnosed with knee OA. All study participants were divided into three research groups: the control group included healthy individuals, the group OA included patients with enrolled cases of OA, and the third group of OA and COVID-19 included patients with OA who recovered from COVID-19 6-9 months ago. The levels of MMPs and TIMP-1 were measured in plasma by enzyme-linked immunosorbent assay.
Results: The study showed a change in the levels of MMPs in patients with OA who had COVID- 19 and those who did not have a history of SARS-CoV-2 infection. Particularly, patients with OA who were infected with coronavirus established an increase in MMP-2, MMP-3, MMP-8, and MMP-9, compared to healthy controls. Compared to normal subjects, a significant decrease in MMP-10 and TIMP-1 was established in both groups of patients with OA and convalescent COVID-19.
Conclusion: Thus, the results suggest that COVID-19 can affect the proteolysis-antiproteolysis system even after a long postinfectious state and may cause complications of existing musculoskeletal pathologies.
Graphical Abstract
[1]
Kapoor C, Vaidya S, Wadhwan V. Hitesh, Kaur G, Pathak A. Seesaw of matrix metalloproteinases (MMPs). J Cancer Res Ther 2016; 12(1): 28-35.
[http://dx.doi.org/10.4103/0973-1482.157337] [PMID: 27072206]
[http://dx.doi.org/10.4103/0973-1482.157337] [PMID: 27072206]
[2]
Bassiouni W, Ali MAM, Schulz R. Multifunctional intracellular matrix metalloproteinases: implications in disease. FEBS J 2021; 288(24): 7162-82.
[http://dx.doi.org/10.1111/febs.15701] [PMID: 33405316]
[http://dx.doi.org/10.1111/febs.15701] [PMID: 33405316]
[3]
Smigiel KS, Parks WC. Matrix metalloproteinases and leukocyte activation. Prog Mol Biol Transl Sci 2017; 147: 167-95.
[http://dx.doi.org/10.1016/bs.pmbts.2017.01.003]
[http://dx.doi.org/10.1016/bs.pmbts.2017.01.003]
[4]
Cabral-Pacheco GA, Garza-Veloz I, Castruita-De la Rosa C, et al. The roles of matrix metalloproteinases and their inhibitors in human diseases. Int J Mol Sci 2020; 21(24): 9739.
[http://dx.doi.org/10.3390/ijms21249739] [PMID: 33419373]
[http://dx.doi.org/10.3390/ijms21249739] [PMID: 33419373]
[5]
Tateiwa D, Yoshikawa H, Kaito T. Cartilage and bone destruction in arthritis: pathogenesis and treatment strategy: A literature review. Cells 2019; 8(8): 818.
[http://dx.doi.org/10.3390/cells8080818] [PMID: 31382539]
[http://dx.doi.org/10.3390/cells8080818] [PMID: 31382539]
[6]
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.
[http://dx.doi.org/10.7759/cureus.18607] [PMID: 34765365]
[http://dx.doi.org/10.7759/cureus.18607] [PMID: 34765365]
[7]
Falalyeyeva T, Pellicano R. Hot topics in chronic inflammation-induced diseases at the time of COVID-19. Minerva Biotechnol Biomol Res 2021; 33(2): 2.
[http://dx.doi.org/10.23736/S2724-542X.21.02803-0]
[http://dx.doi.org/10.23736/S2724-542X.21.02803-0]
[8]
Falalyeyeva T, Komisarenko I, Yanchyshyn A, et al. Vitamin D in the prevention and treatment of type-2 diabetes and associated diseases: a critical view during COVID-19 time. Minerva Biotechnol Biomol Res 2021; 33(2): 65-75.
[http://dx.doi.org/10.23736/S2724-542X.21.02766-X]
[http://dx.doi.org/10.23736/S2724-542X.21.02766-X]
[9]
Fernandez-Patron C, Hardy E. Matrix Metalloproteinases in Health and Disease in the Times of COVID-19. Biomolecules 2022; 12(5): 692.
[http://dx.doi.org/10.3390/biom12050692] [PMID: 35625620]
[http://dx.doi.org/10.3390/biom12050692] [PMID: 35625620]
[10]
Syed F, Li W, Relich RF, et al. Excessive matrix metalloproteinase-1 and hyperactivation of endothelial cells occurred in COVID-19 patients and were associated with the severity of COVID-19. J Infect Dis 2021; 224(1): 60-9.
[http://dx.doi.org/10.1093/infdis/jiab167] [PMID: 33885811]
[http://dx.doi.org/10.1093/infdis/jiab167] [PMID: 33885811]
[11]
Shi S, Su M, Shen G, et al. Matrix metalloproteinase 3 as a valuable marker for patients with COVID‐19. J Med Virol 2021; 93(1): 528-32.
[http://dx.doi.org/10.1002/jmv.26235] [PMID: 32603484]
[http://dx.doi.org/10.1002/jmv.26235] [PMID: 32603484]
[12]
Chavez-Galan L, Ruiz A, Martinez-Espinosa K, et al. Circulating levels of PD-L1, TIM-3 and MMP-7 are promising biomarkers to differentiate COVID-19 patients that require invasive mechanical ventilation. Biomolecules 2022; 12(3): 445.
[http://dx.doi.org/10.3390/biom12030445] [PMID: 35327637]
[http://dx.doi.org/10.3390/biom12030445] [PMID: 35327637]
[13]
D’Avila-Mesquita C, Couto AES, Campos LCB, et al. MMP-2 and MMP-9 levels in plasma are altered and associated with mortality in COVID-19 patients. Biomed Pharmacother 2021; 142: 112067.
[http://dx.doi.org/10.1016/j.biopha.2021.112067] [PMID: 34449310]
[http://dx.doi.org/10.1016/j.biopha.2021.112067] [PMID: 34449310]
[14]
Han Q, Zheng B, Daines L, Sheikh A. Long-term sequelae of COVID-19: A systematic review and meta-analysis of one-year follow-up studies on Post-COVID symptoms. Pathogens 2022; 11(2): 269.
[http://dx.doi.org/10.3390/pathogens11020269] [PMID: 35215212]
[http://dx.doi.org/10.3390/pathogens11020269] [PMID: 35215212]
[15]
Dixit NM, Churchill A, Nsair A, Hsu JJ. Post-Acute COVID-19 Syndrome and the cardiovascular system: What is known? American Heart J Plus: Cardiology Res Pract 2021; 5: 100025.
[http://dx.doi.org/10.1016/j.ahjo.2021.100025] [PMID: 34192289]
[http://dx.doi.org/10.1016/j.ahjo.2021.100025] [PMID: 34192289]
[16]
Raveendran AV, Jayadevan R, Sashidharan S. Long COVID: An overview. Diabetes Metab Syndr 2021; 15(3): 869-75.
[http://dx.doi.org/10.1016/j.dsx.2021.04.007] [PMID: 33892403]
[http://dx.doi.org/10.1016/j.dsx.2021.04.007] [PMID: 33892403]
[17]
Korotkyi O, Dvorshchenko K, Kot L. Oxidative/antioxidant balance and matrix metalloproteinases level in the knee cartilage of rats under experimental osteoarthritis and probiotic administration. Ukr Biochem J 2020; 92(6): 126-36.
[http://dx.doi.org/10.15407/ubj92.06.126]
[http://dx.doi.org/10.15407/ubj92.06.126]
[18]
Korotkyi O, Huet A, Dvorshchenko K, Kobyliak N, Falalyeyeva T, Ostapchenko L. probiotic composition and chondroitin sulfate regulate TLR-2/4-Mediated NF-κB inflammatory pathway and cartilage metabolism in experimental osteoarthritis. Probiotics Antimicrob Proteins 2021; 13(4): 1018-32.
[http://dx.doi.org/10.1007/s12602-020-09735-7] [PMID: 33459997]
[http://dx.doi.org/10.1007/s12602-020-09735-7] [PMID: 33459997]
[19]
Korotkyi OH, Vovk AA, Halenova TI, et al. Cytokines profile in knee cartilage of rats during monoiodoacetate-induced osteoarthritis and administration of probiotic. Biopolim Kletka 2020; 36(1): 22-34.
[http://dx.doi.org/10.7124/bc.000A1E]
[http://dx.doi.org/10.7124/bc.000A1E]
[20]
Korotkyi O, Dvorshchenko K, Vovk A, et al. Effect of probiotic composition on oxidative/antioxidant balance in blood of rats under experimental osteoarthriti. Ukr Biochem J 2019; 91(6): 49-58.
[http://dx.doi.org/10.15407/ubj91.06.049]
[http://dx.doi.org/10.15407/ubj91.06.049]
[21]
Dranitsina AS, Dvorshchenko KO, Korotkyi OH, et al. Expression of Nos2 and Acan genes in rat knee articular cartilage in osteoarthritis. Cytol Genet 2019; 53(6): 481-8.
[http://dx.doi.org/10.3103/S0095452719060021]
[http://dx.doi.org/10.3103/S0095452719060021]
[22]
Cui N, Hu M, Khalil RA. Biochemical and biological attributes of matrix metalloproteinases. Prog Mol Biol Transl Sci 2017; 147: 1-73.
[http://dx.doi.org/10.1016/bs.pmbts.2017.02.005]
[http://dx.doi.org/10.1016/bs.pmbts.2017.02.005]
[23]
Zeng GQ, Chen AB, Li W, Song JH, Gao CY. High MMP-1, MMP-2, and MMP-9 protein levels in osteoarthritis. Genet Mol Res 2015; 14(4): 14811-22.
[http://dx.doi.org/10.4238/2015.November.18.46] [PMID: 26600542]
[http://dx.doi.org/10.4238/2015.November.18.46] [PMID: 26600542]
[24]
Naito K, Takahashi M, Kushida K, et al. Measurement of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases-1 (TIMP-1) in patients with knee osteoarthritis: comparison with generalized osteoarthritis. Rheumatology (Oxford) 1999; 38(6): 510-5.
[http://dx.doi.org/10.1093/rheumatology/38.6.510] [PMID: 10402070]
[http://dx.doi.org/10.1093/rheumatology/38.6.510] [PMID: 10402070]
[25]
Thorson C, Galicia K, Burleson A, et al. Matrix metalloproteinases and their inhibitors and proteoglycan 4 in patients undergoing total joint arthroplasty. Clin Appl Thromb Hemost 2019; 25.
[http://dx.doi.org/10.1177/1076029619828113] [PMID: 30754994]
[http://dx.doi.org/10.1177/1076029619828113] [PMID: 30754994]
[26]
Nees TA, Rosshirt N, Reiner T, Schiltenwolf M, Moradi B. Die Rolle der Inflammation bei Arthroseschmerzen. Schmerz 2019; 33(1): 4-12.
[http://dx.doi.org/10.1007/s00482-018-0346-y] [PMID: 30560495]
[http://dx.doi.org/10.1007/s00482-018-0346-y] [PMID: 30560495]
[27]
Umesh A, Pranay K, Pandey RC, Gupta MK. Evidence mapping and review of long-COVID and its underlying pathophysiological mechanism. Infection 2022; 50(5): 1053-66.
[http://dx.doi.org/10.1007/s15010-022-01835-6] [PMID: 35489015]
[http://dx.doi.org/10.1007/s15010-022-01835-6] [PMID: 35489015]
[28]
da Silva-Neto PV, do Valle VB, Fuzo CA, et al. Matrix metalloproteinases on severe COVID-19 lung disease pathogenesis: Cooperative actions of MMP-8/MMP-2 axis on immune response through HLA-G shedding and oxidative stress. Biomolecules 2022; 12(5): 604.
[http://dx.doi.org/10.3390/biom12050604] [PMID: 35625532]
[http://dx.doi.org/10.3390/biom12050604] [PMID: 35625532]
[29]
Wang M, Zhou Y, Huang W, Zeng Y, Li X. Association between matrix metalloproteinase-1 (MMP-1) protein level and the risk of rheumatoid arthritis and osteoarthritis: a meta-analysis. Braz J Med Biol Res 2021; 54(2): e10366.
[http://dx.doi.org/10.1590/1414-431x202010366] [PMID: 33331536]
[http://dx.doi.org/10.1590/1414-431x202010366] [PMID: 33331536]
[30]
Jarecki J, Małecka-Masalska T, Kosior-Jarecka E, et al. Concentration of selected metalloproteinases and osteocalcin in the serum and synovial fluid of obese women with advanced knee osteoarthritis. Int J Environ Res Public Health 2022; 19(6): 3530.
[http://dx.doi.org/10.3390/ijerph19063530] [PMID: 35329213]
[http://dx.doi.org/10.3390/ijerph19063530] [PMID: 35329213]
[31]
Hwang IY, Youm YS, Cho SD, et al. Synovial fluid levels of TWEAK and matrix metalloproteinase 1 in patients with osteoarthritis, and associations with disease severity. J Orthop Surg (Hong Kong) 2018; 26(1): 2309499018760112.
[http://dx.doi.org/10.1177/2309499018760112] [PMID: 29486670]
[http://dx.doi.org/10.1177/2309499018760112] [PMID: 29486670]
[32]
Koh SM, Chan CK, Teo SH, et al. Elevated plasma and synovial fluid interleukin-8 and interleukin-18 may be associated with the pathogenesis of knee osteoarthritis. Knee 2020; 27(1): 26-35.
[http://dx.doi.org/10.1016/j.knee.2019.10.028] [PMID: 31917106]
[http://dx.doi.org/10.1016/j.knee.2019.10.028] [PMID: 31917106]
[33]
Plsikova Matejova J, Spakova T, Harvanova D, et al. A preliminary study of combined detection of COMP, TIMP-1, and MMP-3 in synovial fluid: Potential indicators of osteoarthritis progression. Cartilage 2021; 13(2) (Suppl.): 1421S-30S.
[http://dx.doi.org/10.1177/1947603520946385] [PMID: 32748631]
[http://dx.doi.org/10.1177/1947603520946385] [PMID: 32748631]
Related Journals
Applied Drug Research, Clinical Trials and Regulatory Affairs
