Matrix metalloproteinases are a promising therapeutic target for the osteoarthritis treatment
DOI: 10.32364/2587-6821-2024-8-7-5
A.V. Tyurin1, I.Z. Gaydukova2, K.E. Akhiyarova1, I.I. Galina1, R.I. Khusainova1,3
1Bashkir State Medical University, Ufa, Russian Federation
2I.I. Mechnikov North-Western State Medical University, St. Petersburg, Russian Federation
3National Medical Research Center of Endocrinology, Moscow, Russian Federation
Osteoarthritis (osteoarthrosis) is one of the most common pathologies of the musculoskeletal system, primarily among the elderly, who present typical clinical symptoms such as joint pain, swelling, stiffness and motion limitation. This can lead to a decrease in physical activity and quality of life, in addition to increasing the socio-economic burden on patients and society as a whole.
According to data from 2017, more than 303 million people worldwide suffer from osteoarthritis, which makes this disease socially significant. Consonant to modern concepts, osteoarthritis is a joint disease characterized by cellular stress and degradation of the extracellular matrix resulting from macro/micro-injuries that activate pathological adaptive restorative responses, including pro-inflammatory pathways of the immune system. A long-term research period into the pathogenesis of this disease did not allow the development of treatment and prevention techniques that would completely solve the problem of osteoarthritis high incidence.
Currently, a pertinent research area is the investigation of this disease phenotypes with particular emphasis on phenotypes associated with inflammation and connective tissue metabolism. An urgent task is to identify the factors regulating these conditions, namely pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukins 1, 6, 18 and catabolism enzymes — matrix metalloproteinases (MMPs), since they can become potential new therapy targets. Most MMPs, including MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10, MMP-13 and MMP-14, are involved in the metabolism of the extracellular matrix and the associated destruction of articular cartilage in osteoarthritis.
This article is devoted to determining the role of inflammatory mediators, MMPs in the osteoarthritis pathogenesis and reviewing new pathogenetically justified treatment options for this disease.
Keywords: osteoarthritis, inflammation, matrix metalloproteinases, therapy targets, connective tissue.
For citation: Tyurin A.V., Gaydukova I.Z., Akhiyarova K.E., Galina I.I., Khusainova R.I. Matrix metalloproteinases are a promising therapeutic target for the osteoarthritis treatment. Russian Medical Inquiry. 2024;8(7):400–405 (in Russ.). DOI: 10.32364/2587-6821-2024-8-7-5.
About the authors:
Anton V. Tyurin — C. Sc. (Med.), Associate Professor, Head of the Department of Internal Diseases and Clinical Psychology, Bashkir State Medical University; 3, Lenin str., Ufa, 450008, Russian Federation; ORCID iD 0000-0002-0841-3024.
Inna Z. Gaydukova — Dr. Sc. (Med.), Associate Professor of the Department of Internal Medicine, Rheumatology, Examination of Temporary Disability Examination and Quality of Medical Care named after E.E. Eichwald, I.I. Mechnikov North-Western State Medical University; 41, Kirochnaya str., St. Petersburg, 191015, Russian Federation; ORCID iD 0000-0003-3500-7256.
Karina E. Akhiyarova — Assistant Professor of the Department of Internal Diseases and Clinical Psychology; Bashkir State Medical University; 3, Lenin str., Ufa, 450008, Russian Federation; ORCID iD 0000-0001-5965-2108.
Ilmira A. Galina — Assistant Professor of the Department of Internal Diseases and Clinical Psychology; Bashkir State Medical University; 3, Lenin str., Ufa, 450008, Russian Federation; ORCID iD 0000-0001-5940-6599.
Rita I. Khusainova — Dr. Sc. (Bio.), Professor of the Department of Internal Diseases and Clinical Psychology, Bashkir State Medical University; 3, Lenin str., Ufa, 450008, Russian Federation; Associate Professor, Chief Researcher of the National Medical Research Center of Endocrinology; 11, Dmitry Ulyanov str., Moscow, 117292, Russian Federation; ORCID iD 0000-0002-8643-850X.
Contact information: Anton V. Tyurin, e-mail: anton.bgmu@gmail.com.
Financial Disclosure: a grant in the form of subsidies from the budget of the Republic of Bashkortostan for the state support of young scientists — postgraduate students and candidates of science (competition code — NOC-GMU-2023).
There is no conflict of interest.
Received 09.06.2024.
Revised 02.07.2024.
Accepted 25.07.2024.
2. Spencer L.J., Dedu A., Kalkidan H.A. et al. Nooshin Abbasi Global, Regional, and National Incidence, Prevalence, and Years Lived with Disability for 354 Diseases and Injuries for 195 Countries and Territories, 1990–2017: A Systematic Analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392:1789–1858. DOI: 10.1016/S0140-6736(18)32279-7.
3. Hu Q., Ecker M. Overview of MMP-13 as a Promising Target for the Treatment of Osteoarthritis. Int J Mol Sci. 2021;22:1–22. DOI: 10.3390/ijms22041742.
4. Altman R., Alarcon G., Appelrouth D. et al. The American College of Rheumatology Criteria for the Classification and Reporting of Osteoarthritis of the Hand. Arthritis Rheum. 1990;33:1601–1610. DOI: 10.1002/art.1780331101.
5. Zhang W., Doherty M., Leeb B.F. et al. EULAR Evidence-Based Recommendations for the Diagnosis of Hand Osteoarthritis: Report of a Task Force of ESCISIT. Ann Rheum Dis. 2009;68:8–17. DOI: 10.1136/ard.2007.084772.
6. Anderson G.P. Endotyping Asthma: New Insights into Key Pathogenic Mechanisms in a Complex, Heterogeneous Disease. Lancet. 2008;372:1107–1119. DOI: 10.1016/S0140-6736(08)61452-X.
7. Steinbeck M.J., Eisenhauer P.T., Maltenfort M.G. et al. Identifying Patient-Specific Pathology in Osteoarthritis Development Based on MicroCT Analysis of Subchondral Trabecular Bone. J Arthroplasty. 2016;31:269–277. DOI: 10.1016/j.arth.2015.08.021.
8. Attur M., Belitskaya-Lévy I., Oh C. et al. Increased Interleukin-1β Gene Expression in Peripheral Blood Leukocytes Is Associated with Increased Pain and Predicts Risk for Progression of Symptomatic Knee Osteoarthritis. Arthritis Rheum. 2011;63:1908–1917. DOI: 10.1002/art.30360.
9. Wyatt L.A., Moreton B.J., Mapp P.I. et al. Histopathological Subgroups in Knee Osteoarthritis. Osteoarthr Cartil. 2017;25:14–22. DOI: 10.1016/j.joca.2016.09.021.
10. Cardoso J.S., Riley J.L., Glover T. et al. Experimental Pain Phenotyping in Community-Dwelling Individuals with Knee Osteoarthritis. Pain. 2016;157:2104–2114. DOI: 10.1097/j.pain.0000000000000625.
11. Лила А.М., Алексеева Л.И., Телышев К.А. Современные подходы к фенотипированию остеоартрита. Современная ревматология. 2019;13(2):4–8. DOI: 10.14412/1996-7012-2019-2-4-8.Lila A.M., Alekseeva L.I., Telyshev K.A. Current Approaches to Osteoarthritis Phenotyping. Sovrem Revmatol. 2019;13:4–8 (in Russ.). DOI: 10.14412/1996-7012-2019-2-4-8.
12. Rowan A.D., Litherland G.J., Hui W., Milner J.M. Metalloproteases as Potential Therapeutic Targets in Arthritis Treatment. Expert Opin. Ther Targets. 2008;12:1–18. DOI: 10.1517/14728222.12.1.1.
13. Howes J.M., Bihan D., Slatter D.A. et al. The Recognition of Collagen and Triple-Helical Toolkit Peptides by MMP-13: Sequence Specificity for Binding and Cleavage. J Biol Chem. 2014;289:24091–24101. DOI: 10.1074/jbc.M114.583443.
14. Mueller M.B., Tuan R.S. Anabolic/Catabolic Balance in Pathogenesis of Osteoarthritis: Identifying Molecular Targets. PM R. 2011;3(6Suppl1):S3-S11. DOI: 10.1016/j.pmrj.2011.05.009.
15. Castrogiovanni P., Di Rosa M., Ravalli S. et al. Moderate Physical Activity as a Prevention Method for Knee Osteoarthritis and the Role of Synoviocytes as Biological Key. Int J Mol Sci. 2019;20(3):511. DOI: 10.3390/ijms20030511.
16. Lanyon P., Muir K., Doherty S., Doherty M. Age and Sex Differences in Hip Joint Space among Asymptomatic Subjects without Structural Change: Implications for Epidemiologic Studies. Arthritis Rheum. 2003;48:1041–1046. DOI: 10.1002/art.10886.
17. Neuhold L.A., Killar L., Zhao W. et al. Postnatal Expression in Hyaline Cartilage of Constitutively Active Human Collagenase-3 (MMP-13) Induces Osteoarthritis in Mice. J Clin Invest. 2001;107:35–44. DOI: 10.1172/JCI10564.
18. Тюрин А.В., Шаповалова Д.А., Лукманова Л.З. и др. Роль полиморфных вариантов генов матриксных металлопротеиназ в формировании нарушения гомеостаза соединительной ткани и патологии опорно-двигательного аппарата. Клиническая медицина. 2018;96(8): 754–761. DOI: 10.18821/0023-2149-2018-96-8-754-761. Tyurin A.V., Shapovalova D.A., Lukmanova L.Z. et al. The Role of Polymorphic Variants of Matrix Metalloproteinases Genes in the Formation of Disruption of Connective Tissue Homeostasis and Pathology of the Musculoskeletal System. Clinical Medicine (Russian Journal). 2018;96(8):754–761 (in Russ.). DOI: 10.18821/0023-2149-2018-96-8-754-761.
19. Gu H., Jiao Y., Yu X. et al. Resveratrol Inhibits the IL-1β-Induced Expression OfMMP-13 and IL-6 in Human Articular Chondrocytes ViaTLR4/MyD88-Dependent and-Independent Signaling Cascades. Int J Mol Med. 2017;39:734–740. DOI: 10.3892/ijmm.2017.2885.
20. Yang Q., Wu S., Mao X. et al. Inhibition Effect of Curcumin on TNF-α and MMP-13 Expression Induced by Advanced Glycation End Products in Chondrocytes. Pharmacology. 2013;91:77–85. DOI: 10.1159/000345345.
21. Rasheed Z., Anbazhagan A.N., Akhtar N. et al. Green Tea Polyphenol Epigallocatechin-3-Gallate Inhibits Advanced Glycation End Product-Induced Expression of Tumor Necrosis Factor-α and Matrix Metalloproteinase-13 in Human Chondrocytes. Arthritis Res Ther. 2009;11(3):R71. DOI: 10.1186/ar2700.
22. Fioranelli M., Roccia M.G., Flavin D., Cota L. Regulation of Inflammatory Reaction in Health and Disease. Int J Mol Sci. 2021;22(10):5277. DOI: 10.3390/ijms22105277.
23. Birnesser H., Klein P., Weiser M. A Modern Homeopathic Medication Works as Well as COX 2 Inhibitors. Der Allg. 2003;25:261–264.
24. Birnesser H., Stolt P. The Homeopathic Antiarthitic Preparation Zeel Comp. N: A Review of Molecular and Clinical Data. Explor J Sci Heal. 2007;3:16–22. DOI: 10.1016/j.explore.2006.10.002.
25. Lozada C.J., del Rio E., Reitberg D.P. et al. A Double-Blind, Randomized, Saline-Controlled Study of the Efficacy and Safety of Co-Administered Intra-Articular Injections of Tr14 and Ze14 for Treatment of Painful Osteoarthritis of the Knee: The MOZArT Trial. Eur J Integr Med. 2017;13:54–63. DOI: 10.1016/j.eujim.2017.07.005.
26. Jäggi R., Würgler U., Grandjean F., Weiser M. Dual Inhibition of 5-Lipoxygenase/Cyclooxygenase by a Reconstituted Homeopathic Remedy; Possible Explanation for Clinical Efficacy and Favourable Gastrointestinal Tolerability. Inflamm Res. 2004;53:150–157. DOI: 10.1007/s00011-003-1236-y.
27. Espanha M.M. Articular Cartilage: Structure and Histochemical Composition. Acta Reumatol Port. 2010;35(5):424–433. PMID: 21245810.
28. Martel-Pelletier J., Boileau C., Pelletier J.P., Roughley P.J. Cartilage in Normal and Osteoarthritis Conditions. Best Pract Res Clin Rheumatol. 2008;22:351–384. DOI: 10.1016/j.berh.2008.02.001.
29. Aigner T., Soeder S., Haag J. IL-1β and BMPS — Interactive Players of Cartilage Matrix Degradation and Regeneration. Eur Cells Mater. 2006;12:49–56. DOI: 10.22203/ecm.v012a06.
30. Yasuda T., Robin Poole A. A Fibronectin Fragment Induces Type II Collagen Degradation by Collagenase through an Interleukin-1-Mediated Pathway. Arthritis Rheum. 2002;46:138–148. DOI: 10.1002/1529-0131(200201)46:1<138::AID-ART10051>3.0.CO;2-K.
31. Schmolz M. Transforming Growth Factor Beta (TGF-β): Eine Neue Regelstrecke Fur Antiphlogistische Therapien? Biol Medizin. 2000;29:31–34. DOI: 10.1016/s1357-2725(97)00128-3.
32. Schmolz M., Heine H. Homöopathische Substanzen Aus Der Antihomotoxischen Medizin Modulieren Die Synthese von TGF-Β1 in Menschlichen Vollblutkulturen. Biol Medizin. 2001;30(2):61–65.
33. Stancikova M., Bely M., Svik K. et al. Effects of Zeel comp. on experimental osteoarthritis in rabbit knee. Rheumatologia. 1999;13(3):101–108.
34. Марьяновский А.А. Механизмы действия препарата Цель Т на патогенетические процессы, лежащие в основе развития остеоартроза. Лечащий врач. 2016;4:38–42.Maryanovsky A.A. Mechanisms of action of the drug Ziel T on the pathogenetic processes underlying the development of osteoarthritis. Attending physician. 2016;4:38–42 (in Russ.).
35. Sanchez C., Hemmer K., Krömmelbein N. et al. Reduction of Matrix Metallopeptidase 13 and Promotion of Chondrogenesis by Zeel T in Primary Human Osteoarthritic Chondrocytes. Front Pharmacol. 2021;12:63504334. DOI: 10.3389/fphar.2021.635034.
36. Sanchez C., Zappia J., Lambert C. et al. Curcuma Longa and Boswellia Serrata Extracts Modulate Different and Complementary Pathways on Human Chondrocytes In Vitro: Deciphering of a Transcriptomic Study. Front Pharmacol. 2022;13:931914. DOI: 10.3389/fphar.2022.931914.
This work is licensed under a Creative Commons «Attribution» 4.0 License.
Распечатать