Novel Biomolecular Target for OA Therapy
DOI:
https://doi.org/10.31282/joti.v4n3.79Kata Kunci:
Osteoartritis, protease, aggrecanase, asam sialatAbstrak
Osteoarthritis (OA) adalah penyakit sendi degeneratif kronis yang diderita oleh banyak orang di seluruh dunia, di mana hilangnya tulang rawan artikular adalah penyebab utama di balik patologi OA. Perubahan anatomis OA meliputi degradasi kartilago, inflamasi sinovium, perubahan tulang subkondral dan pembentukan osteofit. Kerusakan atau hilangnya matriks ekstraseluler (ECM) yang terdiri dari kolagen, proteoglikan dan air merupakan proses patologis OA. Pilihan pengobatan yang tersedia saat ini hanya mencakup Pereda gejala atau penghilang rasa sakit dan prosedur pembedahan berupa penggantian sendi untuk mengoreksi deformitas sebagai komplikasi berat dari OA. Akan tetapi, strategi tersebut tidak memadai untuk memperlambat perkembangan OA, serta tidak sepenuhnya menghentikan atau mengembalikan kerusakan sendi yang telah terjadi. Maka dari itu, baru-baru ini diteliti beberapa alternatif pengobatan OA, termasuk terapi yang menargetkan beberapa enzim dan substrat yang memainkan peran penting dalam OA, yaitu protease, agracanases, matriks metaloproteinase dan asam sialat.
Referensi
Akkiraju H, Nohe A. Role of chondrocytes in cartilage formation, progression of osteoarthritis and cartilage regeneration. J Dev Biol 2015;3:177–92.
Sharma L. Osteoarthritis of the Knee. New England Journal of Medicine 2021;384:51–9. https://doi.org/10.1056/NEJMcp1903768.
Platas J, Guillén MI, del Caz MDP, Gomar F, Mirabet V, Alcaraz MJ. Conditioned media from adipose-tissue-derived mesenchymal stem cells downregulate degradative mediators induced by interleukin-1 β in osteoarthritic chondrocytes. Mediators Inflamm 2013;2013.
Atayde SA, Yoshinari NH, Nascimento DP, Catanozi S, Andrade PC, Velosa APP, et al. Experimental diabetes modulates collagen remodelling of joints in rats. Histol Histopathol 2012;27:1471–9.
McClurg O, Tinson R, Troeberg L. Targeting Cartilage Degradation in Osteoarthritis. Pharmaceuticals 2021;14:126. https://doi.org/10.3390/ph14020126.
Mora JC, Przkora R, Cruz-Almeida Y. Knee osteoarthritis: Pathophysiology and current treatment modalities. J Pain Res 2018;11:2189–96.
Takahata Y, Murakami T, Hata K, Nishimura R. Molecular Mechanisms Involved in the Progression and Protection of Osteoarthritis. Current Molecular Pharmacology 2020;14:165–9. https://doi.org/10.2174/1874467213666200417122933.
Leena Sankari S, Jayasri Krupaa R, Kailash Kumar GM, Balachander N. MMP- Matrix metalloproteinase. Biomed Pharmacol J 2016;9:885–8.
Li H, Wang D, Yuan Y, Min J. New insights on the MMP-13 regulatory network in the pathogenesis of early osteoarthritis. Arthritis Res Ther 2017;19.
Amar S, Smith L, Fields GB. Matrix metalloproteinase collagenolysis in health and disease. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 2017;1864:1940–51. https://doi.org/10.1016/j.bbamcr.2017.04.015.
Yamamoto K, Wilkinson D, Bou-Gharios G. Targeting Dysregulation of Metalloproteinase Activity in Osteoarthritis. Calcified Tissue International 2021;109:277–90. https://doi.org/10.1007/s00223-020-00739-7.
Amar S, Smith L, Fields GB. Matrix metalloproteinase collagenolysis in health and disease. Biochim Biophys Acta Mol Cell Res 2017;1864:1940–51.
Hu Q, Ecker M. Overview of MMP-13 as a Promising Target for the Treatment of Osteoarthritis. International Journal of Molecular Sciences 2021;22:1742. https://doi.org/10.3390/ijms22041742.
Thomson A, Hilkens CMU. Synovial Macrophages in Osteoarthritis: The Key to Understanding Pathogenesis? Frontiers in Immunology 2021;12. https://doi.org/10.3389/fimmu.2021.678757.
Weber KT, Alipui DO, Sison CP, Bloom O, Quraishi S, Overby MC, et al. Serum levels of the proinflammatory cytokine interleukin-6 vary based on diagnoses in individuals with lumbar intervertebral disc diseases. Arthritis Res Ther 2016;18.
Siebuhr AS, Petersen KK, Arendt-Nielsen L, Egsgaard LL, Eskehave T, Christiansen C, et al. Identification and characterisation of osteoarthritis patients with inflammation derived tissue turnover. Osteoarthritis Cartilage 2014;22:44–50.
Succar P, Breen EJ, Kuah D, Herbert BR. Alterations in the Secretome of Clinically Relevant Preparations of Adipose-Derived Mesenchymal Stem Cells Cocultured with Hyaluronan. Stem Cells Int 2015;2015.
D’Arrigo D, Roffi A, Cucchiarini M, Moretti M, Candrian C, Filardo G. Secretome and Extracellular Vesicles as New Biological Therapies for Knee Osteoarthritis: A Systematic Review. J Clin Med 2019;8.
Troeberg L, Lazenbatt C, Anower-E-Khuda MF, Freeman C, Federov O, Habuchi H, et al. Sulfated glycosaminoglycans control the extracellular trafficking and the activity of the metalloprotease inhibitor timp-3. Chem Biol 2014;21:1300–9.
Huang K, Wu LD. Aggrecanase and Aggrecan Degradation in Osteoarthritis: a Review. J Int Med Res 2008;36:1149.
Nagase H, Kashiwagi M. Aggrecanases and cartilage matrix degradation. Arthritis Res Ther 2003;5:94–103.
Bondeson J, Wainwright S, Caterson B, Hughes C. ADAMTS5. Handbook of Proteolytic Enzymes, vol. 1, Elsevier Ltd; 2013, p. 1174–80.
Karsenty G. An Aggrecanase and Osteoarthritis. N Engl J Med 2005;353:522–3.
Apte SS. Anti-ADAMTS5 monoclonal antibodies: Implications for aggrecanase inhibition in osteoarthritis. Biochem J 2016;473:e1–4.
Jiang L, Lin J, Zhao S, Wu J, Jin Y, Yu L, et al. ADAMTS5 in Osteoarthritis: Biological Functions, Regulatory Network, and Potential Targeting Therapies. Frontiers in Molecular Biosciences 2021;8. https://doi.org/10.3389/fmolb.2021.703110.
Schauer R, Kamerling JP. Exploration of the Sialic Acid World, 2018. https://doi.org/10.1016/bs.accb.2018.09.001.
Carpintero-Fernandez P, Varela-Eirin M, Lacetera A, Gago-Fuentes R, Fonseca E, Martin-Santamaria S, et al. New Therapeutic Strategies for Osteoarthritis by Targeting Sialic Acid Receptors. Biomolecules 2020;10. https://doi.org/10.3390/biom10040637.
Carpintero-Fernandez P, Gago-Fuentes R, Varela-Eirin M, Acea B, Fonseca E, Golberg G, et al. Targeting sialic acid modified receptors as a potential therapy for osteoarthritis. Osteoarthritis and Cartilage 2016;24:S334. https://doi.org/10.1016/j.joca.2016.01.598.
Bay-Jensen AC, Kjelgaard-Petersen CF, Petersen KK, Arendt-Nielsen L, Quasnichka HL, Mobasheri A, et al. Aggrecanase degradation of type III collagen is associated with clinical knee pain. Clin Biochem 2018;58:37–43.
Bondeson J, Wainwright S, Hughes C, Caterson B. The regulation of the ADAMTS4 and ADAMTS5 aggrecanases in osteoarthritis: A review. Clin Exp Rheumatol 2008;26:139–45.
