DOI: http://dx.doi.org/10.18203/issn.2455-4510.IntJResOrthop20212441

Role of Undenatured collagen type II and Aflapin combination in the management of osteoarthritis: a review

Karun Jain, Apurv A. Mehra, Kapil D. Mehta, Lyndon Dsouza, Ratna Kumar

Abstract


Osteoarthritis (OA) is the most common joint disease affecting millions worldwide. Osteoarthritis typically affects the knees, hands, hips, and feet. It is characterized by complex pathologic changes in the cartilage which haven’t been fully elucidated yet. However, recent research has shown the involvement of two contributing pathways namely the mechanical and the immune pathways which interlink to cause cartilage destruction. Patients with OA on current treatment options still inevitably progress to a more severe stage becoming candidates for total joint replacement. The cornerstones of OA management in the early stage include exercises, weight loss, education—complemented by topical or oral nonsteroidal anti-inflammatory drugs (NSAIDs) and nutraceuticals like Undenatured type II collagen and Aflapin. Both Undenatured type II collagen and Aflapin offer great promise in OA management by targeting both the immune and mechanical pathways respectively. Undenatured type II collagen works by oral tolerization turning off the immune response in the inflammatory damage (T cell response) against endogenous Type II collagen in the cartilage thus reducing joint inflammation, degradation and stimulates anti-inflammatory cytokine release. Aflapin inhibits 5-LOX and exerts anti-inflammatory action thus providing symptomatic relief of pain and inflammation. This review focusses on the role of mechanical and immune pathways in the pathogenesis of OA and the impact of the combination of Undenatured type-II collagen and Aflapin in targeting these pathways thus improving the clinical outcomes.


Keywords


Aflapin, Undenatured type-II collagen, Pathogenesis, Mechanical pathway, Immune pathway, Osteoarthritis

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References


Chen D, Shen J, Zhao W. Osteoarthritis: toward a comprehensive understanding of pathological mechanism: Bone Research. 2017;5:16044.

Hunter D, Zeinstra SB, Osteoarthritis. Lancet. 2019;393:1745-59.

Lozada C. Progression of Osteoarthritis, Medscape. 2020.

Doherty M. Clinical manifestations and diagnosis of osteoarthritis. 2020.

Yuan. Immunologic Intervention in the Pathogenesis of Osteoarthritis. Arthritis and Rheumatism. 2003;48(3):602-11.

Attur M. Bulletin of the NYU Hospital for Joint Diseases. 2012;70(2):99-108.

Martel-Pelletier J, Wildi LM, Pelletier JP. Future therapeutics for osteoarthritis. Bone. 2012;51(2):297-311.

Westacott CI, Sharif M. Cytokines in osteoarthritis: mediators or markers of joint destruction? Semin Arthritis Rheum. 1996;25:254-72.

Moos V, Fickert S, Muller B, Weber U, Sieper J. Immunohistological analysis of cytokine expression in human osteoarthritic and healthy cartilage. J Rheumatol. 1999; 26:870-9.

Crowley D. Safety and efficacy of undenatured type II collagen in the treatment of osteoarthritis of the knee: a clinical trial. Int J Med Sci. 2009;6(6):312-21.

Tetlow LC, Adlam DJ, Woolley DE. Matrix metalloproteinase and proinflammatory cytokine production by chondrocytes of human osteoarthritic cartilage: associations with degenerative changes. Arthritis Rheum. 2000;44:585-94.

Godessart N, Kunkel SL. Chemokines in autoimmune disease. Curr Opin Immunol 2001; 13:670–5.

Koch AE, Kunkel SL, Shah MR, Fu R, Mazarakis DD, Haines GK, et al. Macrophage inflammatory protein-1: a C-C chemokine in osteoarthritis. Clin Immunol Immunopathol. 1995;77:307-14.

Yuan GH, Masuko-Hongo K, Sakata M, Tsuruha J, Onuma H, Nakamura H, et al. The role of C-C chemokines and their receptors in osteoarthritis. Arthritis Rheum. 2001;44:1056-70.

Glant T, Mikecz K. Antigenic profiles of human, bovine and canine articular chondrocytes. Cell Tissue Res. 1986;244:359-69.

Homandberg GA. Potential regulation of cartilage metabolism in osteoarthritis by fibronectin fragments. Front Biosci. 1999;4:D713-30.

Sokolove J, Lepus CM. Role of inflammation in the pathogenesis of osteoarthritis: latest findings and interpretations. Ther Adv Musculoskeletal Dis. 2013;5(2):77-94.

Ishii H, Yoshino S, Nakamura H, Tsuruha J, Kato T, Nishioka K. Immunophenotyping of synovial activated T cells and expression of Th1/Th2 cytokines in osteoarthritis [abstract]. Arthritis Rheum 1999;42(9):S254.

Kandahari A, Yang X, Dighe A, Pan D, Recognition of Immune Response for the Early Diagnosis and Treatment of Osteoarthritis, J. Immunol Res. 2015;1-13.

Sakata M, Tsuruha JI, Masuko-Hongo K, Nakamura H, Matsui T, Sudo A, et al. Autoantibodies to osteopontin in patients with osteoarthritis and rheumatoid arthritis. J Rheumatol. 2001;28:1492-5.

Jasin HE. Autoantibody specificities of immune complexes sequestered in articular cartilage of patients with rheumatoid arthritis and osteoarthritis. Arthritis Rheum. 1985;28:241-8.

Vishal AA, Mishra A, Raychaudhuri SP. A double blind, randomized, placebo controlled clinical study evaluates the early efficacy of aflapin in subjects with osteoarthritis of knee. Int J Med Sci. 2011;8(7):615-22.

Sengupta K, Krishnaraju AV, Vishal AA. Comparative efficacy and tolerability of 5-Loxin and Aflapin Against osteoarthritis of the knee: a double blind, randomized, placebo controlled clinical study. Int J Med Sci. 2010;7(6):366-77.

Jain AV, Jain KA, N. Vijayaraghavan. AflaB2® and osteoarthritis: a multicentric, observational, postmarketing surveillance study in Indian patients suffering from knee osteoarthritis. Int J Res Orthop. 2021;7(1):1-115.

Lugo JP, Saiyed ZM, Lau FC. Undenatured type II collagen (UC-II®) for joint support: a randomized, double-blind, placebo-controlled study in healthy volunteers. J Int Soc Sports Nutr. 2013;10(1):48.

Lugo JP, Saiyed ZM, Lane NE. Efficacy and tolerability of an undenatured type II collagen supplement in modulating knee osteoarthritis symptoms: a multicenter randomized, double-blind, placebo-controlled study. Nutr J. 2016;15:14.

Bakilan F, Armagan O, Ozgen M. Effects of Native Type II Collagen Treatment on Knee Osteoarthritis: A Randomized Controlled Trial. Eurasian J Med. 2016;48(2):95-101.

Mehra A, Anand P, Borate M. A non-interventional, prospective, multicentric real life Indian study to assess safety and effectiveness of undenatured type 2 collagen in management of osteoarthritis. Int J Res Orthop. 2019;5(2):315-32.

Kolasinski SL, Neogi T, Hochberg MC. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee. Arthritis Care Res (Hoboken). 2020;72(2):149-62.

Bannuru RR, Dasi UR, McAlindon TE. Reassessing the role of acetaminophen in osteoarthritis: Systematic review and meta-analysis. Osteoarthritis Cartilage. 2010;18:S250.

Berenbaum F. Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthr Cartil. 2013;21(1):16-21.

Laev SS, Salakhutdinov NF. Anti-arthritic agents: progress and potential. Bioorg Med Chem. 2015;23(13):3059-80.

Chou R, McDonagh MS, Nakamoto E, Griffin J. Analgesics for Osteoarthritis: An Update of the 2006 Comparative Effectiveness Review [Internet] Rockville (MD): Agency for Healthcare Research and Quality (US). 2011.

Kon E, Filardo G, Drobnic M. Non-surgical management of early knee osteoarthritis. Knee Surg Sports Traumatol Arthrosc. 2012;20(3):436-49.

Bruton LL, Lazo J, Parker KL. Goodman & Gilmans. The Pharmacological Basis of Therapeutics. 11th edition. 2005;438-40.

Roman-Blas JA. CS/GS Combined Therapy Study Group. Combined Treatment With Chondroitin Sulfate and Glucosamine Sulfate Shows No Superiority Over Placebo for Reduction of Joint Pain and Functional Impairment in Patients With Knee Osteoarthritis: A Six-Month Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trial [published correction appears in Arthritis Rheumatol. Arthritis Rheumatol. 2017;69(1):77-85.

Rutjes AW, Jüni P, da Costa BR, Trelle S, Nüesch E, Reichenbach S. Viscosupplementation for osteoarthritis of the knee: a systematic review and meta-analysis. Ann Intern Med. 2012;157:180-91.

Moseley JB, O’Malley K, Petersen NJ, Menke TJ, Brody BA, Kuykendall DH et al. A controlled trial of arthroscopic surgery for osteoarthritis of the knee. N Engl J Med. 2002;347:81-8.

Bakilan. Effects of Native Type II Collagen Treatment on Knee Osteoarthritis: A Randomized Controlled Trial, Eurasian J Med. 2016;48:95-101.

Crowley D. Safety and efficacy of undenatured type II collagen in the treatment of osteoarthritis of the knee: a clinical trial; Int J Med Sci. 2009;6(6):312-21.

Mahajan. Multimodal Anti-inflammatory Approach to Osteoarthritis Management - Review of T Cell Immunomodulation with Undenotured (Native) Collagen Type II, and LOX Inhibition with Boswellia. Nov Tech Arthritis Bone Res. 2019;3(4):555618.

Suva, A flapin: A novel and selective 5-Iipoxygenase inhibitor for arthritis management. Ind. J. Pain. 2018;32 (1):16-23.