Analyze Diet
Animals : an open access journal from MDPI2020; 10(4); doi: 10.3390/ani10040697

Undenatured Type II Collagen (UC-II) in Joint Health and Disease: A Review on the Current Knowledge of Companion Animals.

Abstract: OA is quite common in companion animals, especially in large breed dogs and horses. Collagen, the most abundant protein of mammals, has specific connective tissue types for skin, bones, reticulate, basal lamina, bones, cell surfaces, while type II collagen (UC-II) forms the main structure of cartilage tissue. Even at the smaller dosages, UC-II has also been reported to be more effective than the glucosamine and chondroitin sulfate supplements, which are the supplements most frequently used in the market. In this review, we summarize the effects of UC-II on joint health and function in health and disease conditions in companion animals.
Publication Date: 2020-04-17 PubMed ID: 32316397PubMed Central: PMC7222752DOI: 10.3390/ani10040697Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
  • Journal Article
  • Review

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research article reviews the benefits of undenatured Type II Collagen (UC-II) for joint health in pets, especially large breed dogs and horses, and suggests its effectiveness could outweigh traditional supplements such as glucosamine and chondroitin sulfate.

Understanding the Role of UC-II Collagen in Joint Health

  • Undenatured Type II Collagen (UC-II) is a significant form of collagen that forms the main structure of cartilage tissue in mammals. This cartilage tissue is crucial to joint health as it provides cushion and support for movement.
  • This review discusses how smaller doses of UC-II have been found to be more effective than traditional joint supplements used on the market, namely glucosamine and chondroitin sulfate. This comparison refers to studies where UC-II supplementation led to an improvement in joint pain and mobility in animals.
  • UC-II is particularly useful in managing conditions like Osteoarthritis (OA), which is common in large breed dogs and horses. Osteoarthritis involves the deterioration of cartilage in the joints, often causing pain and limiting movement.

UC-II Collagen and Comparative Effectiveness

  • The researchers highlight that the effectiveness of UC-II, even at smaller doses, suggests its potential in treating joint diseases in animals.
  • Existing options such as glucosamine and chondroitin sulfate supplements have been widely used but may not be as effective as UC-II. These supplements also aid in maintaining and repairing cartilage but research suggests UC-II may offer superior results.
  • The favorable comparison of UC-II to traditional joint supplements opens up new possibilities for animal treatments.

The Relevance of UC-II Collagen Research in Animal Health

  • This review emphasizes the crucial role UC-II could play in the health and well-being of companion animals, particularly those susceptible to joint diseases such as large breed dogs and horses.
  • The evidence suggesting UC-II can improve joint health even in smaller doses presents a significant potential cost advantage, as lower amounts would be needed to achieve the same or even better results compared to other supplements.
  • Future research into UC-II can reveal more about its role and effects in joint health, disease management, and overall animal healthcare protocols.

Cite This Article

APA
Gencoglu H, Orhan C, Sahin E, Sahin K. (2020). Undenatured Type II Collagen (UC-II) in Joint Health and Disease: A Review on the Current Knowledge of Companion Animals. Animals (Basel), 10(4). https://doi.org/10.3390/ani10040697

Publication

ISSN: 2076-2615
NlmUniqueID: 101635614
Country: Switzerland
Language: English
Volume: 10
Issue: 4

Researcher Affiliations

Gencoglu, Hasan
  • Department of Biology, Faculty of Science, Firat University, Elazig (+90) 424, Turkey.
Orhan, Cemal
  • Department of Animal Nutrition, Faculty of Veterinary Medicine, Firat University, Elazig (+90) 424, Turkey.
Sahin, Emre
  • Department of Animal Nutrition, Faculty of Veterinary Medicine, Firat University, Elazig (+90) 424, Turkey.
Sahin, Kazim
  • Department of Animal Nutrition, Faculty of Veterinary Medicine, Firat University, Elazig (+90) 424, Turkey.

Grant Funding

  • 2019-2 / Türkiye Bilimler Akademisi

Conflict of Interest Statement

The authors declare no conflict of interest.

References

This article includes 121 references
  1. Barbosa JD, Lima DHS, Belo-Reis AS, Pinheiro CP, Sousa MGS, Silva JB, Salvarani FM, Oliveira CMC. Degenerative joint disease in cattle and buffaloes in the Amazon region: A retrospective study.. Pesqui. Vet. Bras. 2014;34:845–850.
  2. Iagnocco A. Chapter 14—Osteoarthritis.. In: Wakefield RJ, D’Agostino MA, editors. Essential Applications of Musculoskeletal Ultrasound in Rheumatology. W.B. Saunders; Philadelphia, PA, USA: 2010. pp. 165–180.
  3. Neugebauer V, Han JS, Adwanikar H, Fu Y, Ji G. Techniques for assessing knee joint pain in arthritis.. Mol. Pain 2007;3:8.
    doi: 10.1186/1744-8069-3-8pmc: PMC1851005pubmed: 17391515google scholar: lookup
  4. Serra CI, Soler C. Animal models of osteoarthritis in small mammals.. Vet. Clin. N. Am. Exot. Anim. Pract. 2019;22:211–221.
    doi: 10.1016/j.cvex.2019.01.004pubmed: 30961898google scholar: lookup
  5. McLaughlin RM. Hind limb lameness in the young patient.. Vet. Clin. N. Am. Small Anim. Pract. 2001;31:101–123.
    doi: 10.1016/S0195-5616(01)50040-6pubmed: 11787256google scholar: lookup
  6. Ruff KJ, Kopp KJ, Von Behrens P, Lux M, Mahn M, Back M. Effectiveness of NEM® brand eggshell membrane in the treatment of suboptimal joint function in dogs: A multicenter, randomized, double-blind, placebo-controlled study.. Vet. Med. Res. Rep. 2016;7:113–121.
    doi: 10.2147/VMRR.S101842pmc: PMC6044796pubmed: 30050844google scholar: lookup
  7. Cimino Brown D. What can we learn from osteoarthritis pain in companion animals?. Clin. Exp. Rheumatol. 2017;35(Suppl. 107):53–58.
    pubmed: 28967360
  8. Schachner ER, Lopez MJ. Diagnosis, prevention, and management of canine hip dysplasia: A review.. Vet. Med. Res. Rep. 2015;6:181–192.
    pmc: PMC6070021pubmed: 30101105
  9. O’Neill DG, Church DB, McGreevy PD, Thomson PC, Brodbelt DC. Prevalence of disorders recorded in dogs attending primary-care veterinary practices in England.. PLoS ONE 2014;9:e90501.
  10. Guedes AGP, Meadows JM, Pypendop BH, Johnson EG. Evaluation of tramadol for treatment of osteoarthritis in geriatric cats.. J. Am. Vet. Med. Assoc. 2018;252:565–571.
    doi: 10.2460/javma.252.5.565pubmed: 29461159google scholar: lookup
  11. Contino EK. Management and rehabilitation of joint disease in sport horses.. Vet. Clin. N. Am. Equine Pract. 2018;34:345–358.
    doi: 10.1016/j.cveq.2018.04.007pubmed: 29793734google scholar: lookup
  12. Anderson KL, O’Neill DG, Brodbelt DC, Church DB, Meeson RL, Sargan D, Summers JF, Zulch H, Collins LM. Prevalence, duration and risk factors for appendicular osteoarthritis in a UK dog population under primary veterinary care.. Sci. Rep. 2018;8.
    doi: 10.1038/s41598-018-23940-zpmc: PMC5884849pubmed: 29618832google scholar: lookup
  13. Bland SD. Canine osteoarthritis and treatments: A review.. Vet. Sci. Dev. 2015.
    doi: 10.4081/vsd.2015.5931google scholar: lookup
  14. Chen D, Shen J, Zhao W, Wang T, Han L, Hamilton JL, Im H-J. Osteoarthritis: Toward a comprehensive understanding of pathological mechanism.. Bone Res. 2017;5:16044.
    doi: 10.1038/boneres.2016.44pmc: PMC5240031pubmed: 28149655google scholar: lookup
  15. Mobasheri A, Batt M. An update on the pathophysiology of osteoarthritis.. Ann. Phys. Rehabil. Med. 2016;59:333–339.
    doi: 10.1016/j.rehab.2016.07.004pubmed: 27546496google scholar: lookup
  16. Henrotin Y, Sanchez C, Balligand M. Pharmaceutical and nutraceutical management of canine osteoarthritis: Present and future perspectives.. Vet. J. Lond. Engl. 1997. 2005;170:113–123.
    doi: 10.1016/j.tvjl.2004.08.014pubmed: 15993795google scholar: lookup
  17. Bagi CM, Berryman ER, Teo S, Lane NE. Oral administration of undenatured native chicken type II collagen (UC-II) diminished deterioration of articular cartilage in a rat model of osteoarthritis (OA). Osteoarthr. Cartil. 2017;25:2080–2090.
    doi: 10.1016/j.joca.2017.08.013pubmed: 28888901google scholar: lookup
  18. Aragon CL, Hofmeister EH, Budsberg SC. Systematic review of clinical trials of treatments for osteoarthritis in dogs.. J. Am. Vet. Med. Assoc. 2007;230:514–521.
    doi: 10.2460/javma.230.4.514pubmed: 17302547google scholar: lookup
  19. Beale B. Orthopedic clinical techniques femur fracture repair.. Clin. Technol. Small Anim. Pract. 2004;19:134–150.
    doi: 10.1053/j.ctsap.2004.09.006pubmed: 15712460google scholar: lookup
  20. D’Altilio M, Peal A, Alvey M, Simms C, Curtsinger A, Gupta RC, Canerdy TD, Goad JT, Bagchi M, Bagchi D. therapeutic efficacy and safety of undenatured type II collagen singly or in combination with glucosamine and chondroitin in arthritic dogs.. Toxicol. Mech. Methods. 2007;17:189–196.
    doi: 10.1080/15376510600910469pubmed: 20020968google scholar: lookup
  21. Prabhoo R, Billa G. Undenatured collagen type II for the treatment of osteoarthritis: A review.. Int. J. Res. Orthop. 2018;4:684–689.
  22. Martel-Pelletier J, Boileau C, Pelletier J-P, Roughley PJ. Cartilage in normal and osteoarthritis conditions.. Best Pract. Res. Clin. Rheumatol. 2008;22:351–384.
    doi: 10.1016/j.berh.2008.02.001pubmed: 18455690google scholar: lookup
  23. Collins JA, Diekman BO, Loeser RF. Targeting aging for disease modification in osteoarthritis.. Curr. Opin. Rheumatol. 2018;30:101.
  24. Li Y-S, Xiao W, Luo W. Cellular aging towards osteoarthritis.. Mech. Ageing Dev. 2017;162:80–84.
    doi: 10.1016/j.mad.2016.12.012pubmed: 28049007google scholar: lookup
  25. Rahmati M, Nalesso G, Mobasheri A, Mozafari M. Aging and osteoarthritis: Central role of the extracellular matrix.. Ageing Res. Rev. 2017;40:20–30.
    doi: 10.1016/j.arr.2017.07.004pubmed: 28774716google scholar: lookup
  26. Mobasheri A, Rayman MP, Gualillo O, Sellam J, van der Kraan P, Fearon U. The role of metabolism in the pathogenesis of osteoarthritis.. Nat. Rev. Rheumatol. 2017;13:302–311.
    doi: 10.1038/nrrheum.2017.50pubmed: 28381830google scholar: lookup
  27. Yuan G-H, Masuko-Hongo K, Kato T, Nishioka K. Immunologic intervention in the pathogenesis of osteoarthritis.. Arthritis Rheum. 2003;48:602–611.
    doi: 10.1002/art.10768pubmed: 12632410google scholar: lookup
  28. Poole A, Kobayashi M, Yasuda T, Laverty S, Mwale F, Kojima T, Sakai T, Wahl C, El-Maadawy S, Webb G. Type II collagen degradation and its regulation in articular cartilage in osteoarthritis.. Ann. Rheum. Dis. 2002;61:ii78–ii81.
    doi: 10.1136/ard.61.suppl_2.ii78pmc: PMC1766700pubmed: 12379630google scholar: lookup
  29. Sandell LJ, Aigner T. Articular cartilage and changes in Arthritis: Cell biology of osteoarthritis.. Arthritis Res. 2001;3:107–113.
    doi: 10.1186/ar148pmc: PMC128887pubmed: 11178118google scholar: lookup
  30. Pelletier J-P, Martel-Pelletier J, Abramson SB. Osteoarthritis, an inflammatory disease: Potential implication for the selection of new therapeutic targets.. Arthritis Rheum. 2001;44:1237–1247.
  31. Abramson SB, Attur M, Amin AR, Clancy R. Nitric oxide and inflammatory mediators in the perpetuation of osteoarthritis.. Curr. Rheumatol. Rep. 2001;3:535–541.
    doi: 10.1007/s11926-001-0069-3pubmed: 11709117google scholar: lookup
  32. Amin AR, Dave M, Attur M, Abramson SB. COX-2, NO, and cartilage damage and repair.. Curr. Rheumatol. Rep. 2000;2:447–453.
    doi: 10.1007/s11926-000-0019-5pubmed: 11123096google scholar: lookup
  33. Moreland LW. Intra-articular hyaluronan (hyaluronic acid) and hylans for the treatment of osteoarthritis: Mechanisms of action.. Arthritis Res Ther. 2003;5:54.
    doi: 10.1186/ar623pmc: PMC165033pubmed: 12718745google scholar: lookup
  34. Mehana E-SE, Khafaga AF, El-Blehi SS. The role of matrix metalloproteinases in osteoarthritis pathogenesis: An updated review.. Life Sci. 2019;234:116786.
    doi: 10.1016/j.lfs.2019.116786pubmed: 31445934google scholar: lookup
  35. Nagase H, Kashiwagi M. Aggrecanases and cartilage matrix degradation.. Arthritis Res. Ther. 2003;5:94.
    doi: 10.1186/ar630pmc: PMC165039pubmed: 12718749google scholar: lookup
  36. Poole AR. An introduction to the pathophysiology of osteoarthritis.. Front. Biosci. J. Virtual Libr. 1999;4:D662–D670.
    doi: 10.2741/A463pubmed: 10525481google scholar: lookup
  37. Pelletier J-P, Caron JP, Evans C, Robbins PD, Georgescu HI, Jovanovic D, Fernandes JC, Martel-Pelletier J. In vivo suppression of early experimental osteoarthritis by interleukin-1 receptor antagonist using gene therapy.. Arthritis Rheum. 1997;40:1012–1019.
    doi: 10.1002/art.1780400604pubmed: 9182910google scholar: lookup
  38. Cicero AF, Laghi L. Activity and potential role of licofelone in the management of osteoarthritis.. Clin. Interv. Aging. 2007;2:73–79.
    doi: 10.2147/ciia.2007.2.1.73pmc: PMC2684079pubmed: 18044077google scholar: lookup
  39. Pelletier J-P, Boileau C, Boily M, Brunet J, Mineau F, Geng C, Reboul P, Laufer S, Lajeunesse D, Martel-Pelletier J. The protective effect of licofelone on experimental osteoarthritis is correlated with the downregulation of gene expression and protein synthesis of several major cartilage catabolic factors: MMP-13, cathepsin K and aggrecanases.. Arthritis Res. Ther. 2005;7:R1091–R1102.
    doi: 10.1186/ar1788pmc: PMC1257437pubmed: 16207326google scholar: lookup
  40. Jovanovic DV, Fernandes JC, Martel-Pelletier J, Jolicoeur FC, Reboul P, Laufer S, Tries S, Pelletier J-P. In vivo dual inhibition of cyclooxygenase and lipoxygenase by ML-3000 reduces the progression of experimental osteoarthritis: Suppression of collagenase 1 and interleukin-1beta synthesis.. Arthritis Rheum. 2001;44:2320–2330.
  41. Zhang W, Ouyang H, Dass CR, Xu J. Current research on pharmacologic and regenerative therapies for osteoarthritis.. Bone Res. 2016;4:15040.
    doi: 10.1038/boneres.2015.40pmc: PMC4772471pubmed: 26962464google scholar: lookup
  42. Jafarzadeh SR, Felson DT. Updated estimates suggest a much higher prevalence of arthritis in United States adults than previous ones.. Arthritis Rheumatol. 2018;70:185–192.
    doi: 10.1002/art.40355pmc: PMC5788727pubmed: 29178176google scholar: lookup
  43. Bhathal A, Spryszak M, Louizos C, Frankel G. Glucosamine and chondroitin use in canines for osteoarthritis: A review.. Open Vet. J. 2017;7:36.
    doi: 10.4314/ovj.v7i1.6pmc: PMC5356289pubmed: 28331832google scholar: lookup
  44. Liu X, Machado GC, Eyles JP, Ravi V, Hunter DJ. Dietary supplements for treating osteoarthritis: A systematic review and meta-analysis.. Br. J. Sports Med. 2018;52:167–175.
    doi: 10.1136/bjsports-2016-097333pubmed: 29018060google scholar: lookup
  45. Sahin K, Perez Ojalvo S, Akdemir F, Orhan C, Tuzcu M, Sahin N, Ozercan IH, Sylla S, Koca SS, Yilmaz I. Effect of inositol -stabilized arginine silicate on arthritis in a rat model.. Food Chem. Toxicol. Int. J. Publ. Br. Ind. Biol. Res. Assoc. 2019;125:242–251.
    doi: 10.1016/j.fct.2019.01.005pubmed: 30634014google scholar: lookup
  46. Sophia Fox AJ, Bedi A, Rodeo SA. The basic science of articular cartilage.. Sports Health 2009;1:461–468.
    doi: 10.1177/1941738109350438pmc: PMC3445147pubmed: 23015907google scholar: lookup
  47. Pelletier J-P, Martel-Pelletier J, Raynauld J-P. Most recent developments in strategies to reduce the progression of structural changes in osteoarthritis: Today and tomorrow.. Arthritis Res. Ther. 2006;8:206.
    doi: 10.1186/ar1932pmc: PMC1526599pubmed: 16569256google scholar: lookup
  48. Gordon MK, Hahn RA. Collagens.. Cell Tissue Res. 2010;339:247–257.
    doi: 10.1007/s00441-009-0844-4pmc: PMC2997103pubmed: 19693541google scholar: lookup
  49. Bagchi D, Misner B, Bagchi M, Kothari SC, Downs BW, Fafard RD, Preuss HG. Effects of orally administered undenatured type II collagen against arthritic inflammatory diseases: A mechanistic exploration.. Int. J. Clin. Pharmacol. Res. 2002;22:101–110.
    pubmed: 12837047
  50. Lerman RH, Chang J-L, Konda V, Desai A, Montalto MB. Nutritional approach for relief of joint discomfort: A 12-week, open-case series and illustrative case report.. Integr. Med. 2015;14:10.
    pmc: PMC4712866pubmed: 26770167
  51. Tong T, Zhao W, Wu Y-Q, Chang Y, Wang Q-T, Zhang L-L, Wei W. Chicken type II collagen induced immune balance of main subtype of helper T cells in mesenteric lymph node lymphocytes in rats with collagen-induced arthritis.. Inflamm. Res. Off. J. Eur. Histamine Res. Soc. 2010;59:369–377.
    doi: 10.1007/s00011-009-0109-4pubmed: 19862478google scholar: lookup
  52. Nagler-Anderson C, Bober LA, Robinson ME, Siskind GW, Thorbecke GJ. Suppression of type II collagen-induced arthritis by intragastric administration of soluble type II collagen.. Proc. Natl. Acad. Sci. USA 1986;83:7443–7446.
    doi: 10.1073/pnas.83.19.7443pmc: PMC386734pubmed: 3463976google scholar: lookup
  53. Asnagli H, Martire D, Belmonte N, Quentin J, Bastian H, Boucard-Jourdin M, Fall PB, Mausset-Bonnefont A-L, Mantello-Moreau A, Rouquier S. Type 1 regulatory T cells specific for collagen type II as an efficient cell-based therapy in arthritis.. Arthritis Res. Ther. 2014;16:R115.
    doi: 10.1186/ar4567pmc: PMC4075412pubmed: 24886976google scholar: lookup
  54. Müller RD, John T, Kohl B, Oberholzer A, Gust T, Hostmann A, Hellmuth M, Laface D, Hutchins B, Laube G. IL-10 overexpression differentially affects cartilage matrix gene expression in response to TNF-alpha in human articular chondrocytes in vitro.. Cytokine 2008;44:377–385.
    doi: 10.1016/j.cyto.2008.10.012pubmed: 19026560google scholar: lookup
  55. Steinmeyer J. Pharmacological basis for the therapy of pain and inflammation with nonsteroidal anti-inflammatory drugs.. Arthritis Res. 2000;2:379–385.
    doi: 10.1186/ar116pmc: PMC130140pubmed: 11094452google scholar: lookup
  56. Marshall S, Bacote V, Traxinger RR. Discovery of a metabolic pathway mediating glucose-induced desensitization of the glucose transport system. Role of hexosamine biosynthesis in the induction of insulin resistance.. J. Biol. Chem. 1991;266:4706–4712.
    pubmed: 2002019
  57. Simon RR, Marks V, Leeds AR, Anderson JW. A comprehensive review of oral glucosamine use and effects on glucose metabolism in normal and diabetic individuals.. Diabetes Metab. Res. Rev. 2011;27:14–27.
    doi: 10.1002/dmrr.1150pmc: PMC3042150pubmed: 21218504google scholar: lookup
  58. Patti ME, Virkamäki A, Landaker EJ, Kahn CR, Yki-Järvinen H. Activation of the hexosamine pathway by glucosamine in vivo induces insulin resistance of early postreceptor insulin signaling events in skeletal muscle.. Diabetes 1999;48:1562–1571.
    doi: 10.2337/diabetes.48.8.1562pubmed: 10426374google scholar: lookup
  59. Rossetti L, Hawkins M, Chen W, Gindi J, Barzilai N. In vivo glucosamine infusion induces insulin resistance in normoglycemic but not in hyperglycemic conscious rats.. J. Clin. Investig. 1995;96:132–140.
    doi: 10.1172/JCI118013pmc: PMC185181pubmed: 7615783google scholar: lookup
  60. Ando A, Hagiwara Y, Chimoto E, Hatori K, Onoda Y, Itoi E. Intra-articular injection of hyaluronan diminishes loss of chondrocytes in a rat immobilized-knee model.. Tohoku J. Exp. Med. 2008;215:321–331.
    doi: 10.1620/tjem.215.321pubmed: 18679006google scholar: lookup
  61. Rausch-Derra L, Huebner M, Wofford J, Rhodes L. A prospective, randomized, masked, placebo-controlled multisite clinical study of grapiprant, an EP4 Prostaglandin Receptor Antagonist (PRA), in dogs with osteoarthritis.. J. Vet. Intern. Med. 2016;30:756–763.
    doi: 10.1111/jvim.13948pmc: PMC4913586pubmed: 27075237google scholar: lookup
  62. Bergh MS, Budsberg SC. The coxib NSAIDs: Potential clinical and pharmacologic importance in veterinary medicine.. J. Vet. Intern. Med. 2005;19:633–643.
  63. KuKanich B, Bidgood T, Knesl O. Clinical pharmacology of nonsteroidal anti-inflammatory drugs in dogs.. Vet. Anaesth. Analg. 2012;39:69–90.
  64. Ho KY, Gwee KA, Cheng YK, Yoon KH, Hee HT, Omar AR. Nonsteroidal anti-inflammatory drugs in chronic pain: Implications of new data for clinical practice.. J. Pain Res. 2018;11:1937–1948.
    doi: 10.2147/JPR.S168188pmc: PMC6160277pubmed: 30288088google scholar: lookup
  65. Jerosch J. Effects of glucosamine and chondroitin sulfate on cartilage metabolism in OA: Outlook on other nutrient partners especially omega-3 fatty acids.. Int. J. Rheumatol. 2011;2011:969012.
    doi: 10.1155/2011/969012pmc: PMC3150191pubmed: 21826146google scholar: lookup
  66. Copeland RJ, Bullen JW, Hart GW. Cross-talk between GlcNAcylation and phosphorylation: Roles in insulin resistance and glucose toxicity.. Am. J. Physiol. Endocrinol. Metab. 2008;295:E17–E28.
    doi: 10.1152/ajpendo.90281.2008pmc: PMC3751035pubmed: 18445751google scholar: lookup
  67. Zhou P-H, Liu S-Q, Peng H. The effect of hyaluronic acid on IL-1beta-induced chondrocyte apoptosis in a rat model of osteoarthritis.. J. Orthop. Res. Off. Publ. Orthop. Res. Soc. 2008;26:1643–1648.
    doi: 10.1002/jor.20683pubmed: 18524010google scholar: lookup
  68. Peal A, D’Altilio M, Simms C, Alvey M, Gupta RC, Goad JT, Canerdy TD, Bagchi M, Bagchi D. Therapeutic efficacy and safety of undenatured type-II collagen (UC-II) alone or in combination with (-)-hydroxycitric acid and chromemate in arthritic dogs.. J. Vet. Pharmacol. Ther. 2007;30:275–278.
  69. Deparle LA, Gupta RC, Canerdy TD, Goad JT, D’Altilio M, Bagchi M, Bagchi D. Efficacy and safety of glycosylated undenatured type-II collagen (UC-II) in therapy of arthritic dogs.. J. Vet. Pharmacol. Ther. 2005;28:385–390.
  70. Bagchi M, Stocker A, Burke R, Wedgeford K, Gupta RC, Canerdy TD, Goad JT, Barnett D, Bagchi D. Efficacy and safety of undenatured type II collagen (UC-II) in arthritic horses.. Toxicol. Lett. 2007;172:S223.
  71. Crowley DC, Lau FC, Sharma P, Evans M, Guthrie N, Bagchi M, Bagchi D, Dey DK, Raychaudhuri SP. Safety and efficacy of undenatured type II collagen in the treatment of osteoarthritis of the knee: A clinical trial.. Int. J. Med. Sci. 2009:312–321.
    doi: 10.7150/ijms.6.312pmc: PMC2764342pubmed: 19847319google scholar: lookup
  72. Gupta RC, Canerdy TD, Skaggs P, Stocker A, Zyrkowski G, Burke R, Wegford K, Goad JT, Rohde K, Barnett D. Therapeutic efficacy of undenatured type-II collagen (UC-II) in comparison to glucosamine and chondroitin in arthritic horses.. J. Vet. Pharmacol. Ther. 2009;32:577–584.
  73. Bagchi M, Gupta R, Lindley J, Barnes M, Canerdy T, Goad J, Bagchi D. Suppression of arthritic pain in dogs by undenatured type-II collagen (UC-II) treatment quantitatively assessed by ground force plate.. Toxicol. Lett. 2009;189:S231.
  74. Gupta RC, Canerdy TD, Lindley J, Konemann M, Minniear J, Carroll BA, Hendrick C, Goad JT, Rohde K, Doss R. Comparative therapeutic efficacy and safety of type-II collagen (uc-II), glucosamine and chondroitin in arthritic dogs: Pain evaluation by ground force plate: Arthritis treatment in dogs.. J. Anim. Physiol. Anim. Nutr. 2012;96:770–777.
  75. Lugo JP, Saiyed ZM, Lau FC, Molina JPL, Pakdaman MN, Shamie A, Udani JK. 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;10:48.
    doi: 10.1186/1550-2783-10-48pmc: PMC4015808pubmed: 24153020google scholar: lookup
  76. 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. 2015;15:14.
    doi: 10.1186/s12937-016-0130-8pmc: PMC4731911pubmed: 26822714google scholar: lookup
  77. Blair JL, Bonavaud S. Palatability and tolerability of a novel joint supplement in the cat. Clinical/research abstracts accepted for presentation at the World Feline Congress 2017.. J. Feline Med. Surg. 2017;19:961–969.
    pubmed: 0
  78. Samarelli R, Stabile M, Fracassi L. Use of UC-II (Undenaturated Type II Collagen) in Management of Osteoarthritis in Dogs: A Clinical Trial.. Università degli Studi; Torino, Italy: 2018.
  79. Stabile M, Samarelli R, Trerotoli P, Fracassi L, Lacitignola L, Crovace A, Staffieri F. Evaluation of the effects of undenatured type II collagen (UC-II) as compared to robenacoxib on the mobility impairment induced by osteoarthritis in dogs.. Vet. Sci. 2019;6:72.
    doi: 10.3390/vetsci6030072pmc: PMC6789547pubmed: 31487772google scholar: lookup
  80. Mehra A, Anand P, Borate M, Paul P, Kamble S, Mehta KD, Qamra A, Shah A, Jain R. A non-interventional, prospective, multicentric real life Indian study to assess safety and effectiveness of un-denatured type 2 collagen in management of osteoarthritis.. Int. J. Res. Orthop. 2019;5:315–320.
  81. Azeem MA, Patil R. The Study of undenatured type II collagen in the knee osteoarthritis.. Int. J. Orthop. 2019;5:4.
  82. Meeson RL, Todhunter RJ, Blunn G, Nuki G, Pitsillides AA. Spontaneous dog osteoarthritis—A One Medicine vision.. Nat. Rev. Rheumatol. 2019;15:273–287.
    doi: 10.1038/s41584-019-0202-1pmc: PMC7097182pubmed: 30953036google scholar: lookup
  83. King LK, March L, Anandacoomarasamy A. Obesity & osteoarthritis.. Indian J. Med. Res. 2013;138:185–193.
    pmc: PMC3788203pubmed: 24056594
  84. Man G, Mologhianu G. Osteoarthritis pathogenesis—A complex process that involves the entire joint.. J. Med. Life. 2014;7:37–41.
    pmc: PMC3956093pubmed: 24653755
  85. Grandalen J, Lingaas F. Arthrosis in the elbow joint of young rapidly growing dogs: A genetic investigation.. J. Small Anim. Pract. 1991;32:460–464.
  86. Alam MR, Lee HB, Kim MS, Kim N. Surgical model of osteoarthritis secondary to medial patellar luxation in dogs.. Vet. Med. 2018;53:123–130.
    doi: 10.17221/3155-VETMEDgoogle scholar: lookup
  87. Rychel JK. Diagnosis and treatment of osteoarthritis.. Top. Companion Anim. Med. 2010;25:20–25.
    doi: 10.1053/j.tcam.2009.10.005pubmed: 20188335google scholar: lookup
  88. Mele E. Epidemiology of osteoarthritis.. Vet. Focus. 2007;17:4–10.
    doi: 10.1055/s-0034-1381772google scholar: lookup
  89. Pettitt RA, German AJ. Investigation and management of canine osteoarthritis.. Practice 2015;37:1–8.
    doi: 10.1136/inp.h5763google scholar: lookup
  90. Smith GK, Paster ER, Powers MY, Lawler DF, Biery DN, Shofer FS, McKelvie PJ, Kealy RD. Lifelong diet restriction and radiographic evidence of osteoarthritis of the hip joint in dogs.. J. Am. Vet. Med. Assoc. 2006;229:690–693.
    doi: 10.2460/javma.229.5.690pubmed: 16948575google scholar: lookup
  91. Johnston SA. Osteoarthritis. Joint anatomy, physiology, and pathobiology.. Vet. Clin. N. Am. Small Anim. Pract. 1997;27:699–723.
    doi: 10.1016/S0195-5616(97)50076-3pubmed: 9243777google scholar: lookup
  92. Goh S-L, Persson MSM, Stocks J, Hou Y, Welton NJ, Lin J, Hall MC, Doherty M, Zhang W. Relative efficacy of different exercises for pain, function, performance and quality of life in knee and hip osteoarthritis: Systematic review and network meta-analysis.. Sports Med. 2019;49:743–761.
    doi: 10.1007/s40279-019-01082-0pmc: PMC6459784pubmed: 30830561google scholar: lookup
  93. Lascelles BDX, Knazovicky D, Case B, Freire M, Innes JF, Drew AC, Gearing DP. A canine-specific anti-nerve growth factor antibody alleviates pain and improves mobility and function in dogs with degenerative joint disease-associated pain.. BMC Vet. Res. 2015;11:101.
    doi: 10.1186/s12917-015-0413-xpmc: PMC4419463pubmed: 25926287google scholar: lookup
  94. Comblain F, Serisier S, Barthelemy N, Balligand M, Henrotin Y. Review of dietary supplements for the management of osteoarthritis in dogs in studies from 2004 to 2014.. J. Vet. Pharmacol. Ther. 2016;39:1–15.
    doi: 10.1111/jvp.12251pubmed: 26205697google scholar: lookup
  95. Sieper J, Kary S, Sörensen H, Alten R, Eggens U, Hüge W, Hiepe F, Kühne A, Listing J, Ulbrich N. Oral type II collagen treatment in early rheumatoid arthritis. A double-blind, placebo-controlled, randomized trial.. Arthritis Rheum. 1996;39:41–51.
    doi: 10.1002/art.1780390106pubmed: 8546737google scholar: lookup
  96. Trentham DE, Dynesius-Trentham RA, Orav EJ, Combitchi D, Lorenzo C, Sewell KL, Hafler DA, Weiner HL. Effects of oral administration of type II collagen on rheumatoid arthritis.. Science 1993;261:1727–1730.
    doi: 10.1126/science.8378772pubmed: 8378772google scholar: lookup
  97. Park K-S, Park M-J, Cho M-L, Kwok S-K, Ju J-H, Ko H-J, Park S-H, Kim H-Y. Type II collagen oral tolerance; mechanism and role in collagen-induced arthritis and rheumatoid arthritis.. Mod. Rheumatol. 2009;19:581–589.
    doi: 10.3109/s10165-009-0210-0pubmed: 19697097google scholar: lookup
  98. Yoshinari O, Moriyama H, Shiojima Y. An overview of a novel, water-soluble undenatured type II collagen (NEXT-II). J. Am. Coll. Nutr. 2015;34:255–262.
    doi: 10.1080/07315724.2014.919541pubmed: 25751538google scholar: lookup
  99. Yoshinari O, Shiojima Y, Moriyama H, Shinozaki J, Nakane T, Masuda K, Bagchi M. Water-soluble undenatured type II collagen ameliorates collagen-induced arthritis in mice.. J. Med. Food. 2013;16:1039–1045.
    doi: 10.1089/jmf.2013.2911pubmed: 24175655google scholar: lookup
  100. Caron JP. Chapter 63—Osteoarthritis.. In: Ross MW, Dyson SJ, editors. Diagnosis and Management of Lameness in the Horse. W.B. Saunders; Saint Louis, MO, USA: 2003. pp. 572–591.
  101. Ireland JL, Wylie CE, Collins SN, Verheyen KLP, Newton JR. Preventive health care and owner-reported disease prevalence of horses and ponies in Great Britain.. Res. Vet. Sci. 2013;95:418–424.
    doi: 10.1016/j.rvsc.2013.05.007pubmed: 23768693google scholar: lookup
  102. Van Weeren PR, Back W. Musculoskeletal disease in aged horses and its management.. Vet. Clin. N. Am. Equine Pract. 2016;32:229–247.
    doi: 10.1016/j.cveq.2016.04.003pubmed: 27449390google scholar: lookup
  103. Da Garcia RS, de Melo UP, Ferreira C, dos Toscano FS, da Cruz GM. Estudo clínico e radiográfico da osteoartrite társica juvenil em potros da raça mangalarga marchador.. Ciênc. Anim. Bras. 2009;10:254–260.
  104. Kawcak CE, McIlwraith CW, Norrdin RW, Park RD, James SP. The role of subchondral bone in joint disease: A review.. Equine Vet. J. 2001;33:120–126.
  105. Riggs CM, Whitehouse GH, Boyde A. Pathology of the distal condyles of the third metacarpal and third metatarsal bones of the horse.. Equine Vet. J. 1999;31:140–148.
  106. Neundorf RH, Lowerison MB, Cruz AM, Thomason JJ, McEwen BJ, Hurtig MB. Determination of the prevalence and severity of metacarpophalangeal joint osteoarthritis in Thoroughbred racehorses via quantitative macroscopic evaluation.. Am. J. Vet. Res. 2010;71:1284–1293.
    doi: 10.2460/ajvr.71.11.1284pubmed: 21034319google scholar: lookup
  107. Egenvall A, Penell JC, Bonnett BN, Olson P, Pringle J. Mortality of Swedish horses with complete life insurance between 1997 and 2000: Variations with sex, age, breed and diagnosis.. Vet. Rec. 2006;158:397–406.
    doi: 10.1136/vr.158.12.397pubmed: 16565338google scholar: lookup
  108. Klinck MP, Frank D, Guillot M, Troncy E. Owner-perceived signs and veterinary diagnosis in 50 cases of feline osteoarthritis.. Can. Vet. J. 2012;53:1181–1186.
    pmc: PMC3474573pubmed: 23633711
  109. Stamper C. Osteoarthritis in cats: A more common disease than you might expect.. FDA 2008;23:6–8.
  110. Lascelles BDX. Feline degenerative joint disease.. Vet. Surg. 2010;39:2–13.
  111. Bennett D, Zainal Ariffin SM, Johnston P. Osteoarthritis in the cat: 1. how common is it and how easy to recognise?. J. Feline Med. Surg. 2012;14:65–75.
    doi: 10.1177/1098612X11432828pmc: PMC11148909pubmed: 22247326google scholar: lookup
  112. Clarke SP, Mellor D, Clements DN, Gemmill T, Farrell M, Carmichael S, Bennett D. Prevalence of radiographic signs of degenerative joint disease in a hospital population of cats.. Vet. Rec. 2005;157:793–799.
    doi: 10.1136/vr.157.25.793pubmed: 16361472google scholar: lookup
  113. Godfrey DR. Osteoarthritis in cats: A retrospective radiological study.. J. Small Anim. Pract. 2005;46:425–429.
  114. Hardie EM, Roe SC, Martin FR. Radiographic evidence of degenerative joint disease in geriatric cats: 100 cases (1994–1997). J. Am. Vet. Med. Assoc. 2002;220:628–632.
    doi: 10.2460/javma.2002.220.628pubmed: 12418522google scholar: lookup
  115. Slingerland LI, Hazewinkel HW, Meij BP, Picavet P, Voorhout G. Cross-sectional study of the prevalence and clinical features of osteoarthritis in 100 cats.. Vet. J. Lond. Engl. 2011;187:304–309.
    doi: 10.1016/j.tvjl.2009.12.014pubmed: 20083417google scholar: lookup
  116. Schadow S, Siebert H-C, Lochnit G, Kordelle J, Rickert M, Steinmeyer J. Collagen metabolism of human osteoarthritic articular cartilage as modulated by bovine collagen hydrolysates.. PLoS ONE 2013;8:e53955.
  117. European Food Safety Authority (EFSA). Opinion of the Scientific Panel on biological hazards (BIOHAZ) on the safety of collagen and a processing method for the production of collagen.. EFSA J. 2005;3:174.
    doi: 10.2903/j.efsa.2005.174google scholar: lookup
  118. Walrand S, Chiotelli E, Noirt F, Mwewa S, Lassel T. Consumption of a functional fermented milk containing collagen hydrolysate improves the concentration of collagen-specific amino acids in plasma.. J. Agric. Food Chem. 2008;56:7790–7795.
    doi: 10.1021/jf800691fpubmed: 18707117google scholar: lookup
  119. Lugo JP. Letter to the editor UC-II® Undenatured type II collagen: Update to analytical methods.. J. Int. Soc. Sports Nutr. 2019;16:29.
    doi: 10.1186/s12970-019-0298-3pmc: PMC6636149pubmed: 31311550google scholar: lookup
  120. Marone PA, Lau FC, Gupta RC, Bagchi M, Bagchi D. Safety and toxicological evaluation of undenatured type II collagen.. Toxicol. Mech. Methods. 2010;20:175–189.
    doi: 10.3109/15376511003646440pubmed: 20170336google scholar: lookup
  121. InterHealth’s UC-II® Receives GRAS Status. [(accessed on 14 October 2019)]; Available online: https://www.newhope.com/food-amp-beverage/interhealths-uc-ii-receives-gras-status.