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Home / Equine Research Bank / Animals (Basel) / Role of Innate Immunity in Initiation and Progression of Ost...
Animals : an open access journal from MDPI2021; 11(11); 3247; doi: 10.3390/ani11113247

Role of Innate Immunity in Initiation and Progression of Osteoarthritis, with Emphasis on Horses.

Abstract: Osteoarthritis (OA) is a common condition with diverse etiologies, affecting horses, humans, and companion animals. Importantly, OA is not a single disease, but rather a disease process initiated by different events, including acute trauma, irregular or repetitive overload of articular structures, and spontaneous development with aging. Our understanding of the pathogenesis of OA is still evolving, and OA is increasingly considered a multifactorial disease in which the innate immune system plays a key role in regulating and perpetuating low-grade inflammation, resulting in sustained cartilage injury and destruction. Macrophages within the synovium and synovial fluid are considered the key regulators of immune processes in OA and are capable of both stimulating and suppressing joint inflammation, by responding to local and systemic cues. The purpose of this review is to examine the role of the innate immune system in the overall pathogenesis of OA, drawing on insights from studies in humans, animal models of OA, and from clinical and research studies in horses. This review also discusses the various therapeutic immune modulatory options currently available for managing OA and their mechanisms of action.
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Publication Date: 2021-11-13 PubMed ID: 34827979PubMed Central: PMC8614551DOI: 10.3390/ani11113247Google Scholar: Lookup
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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.

The research article focuses on the role of the innate immune system in the onset and progression of osteoarthritis in horses, with additional insights derived from human and animal model studies.

Understanding Osteoarthritis

  • Osteoarthritis (OA) is a prevalent condition affecting various species, including horses, humans, and other animals. It is not distinct as an illness but rather characterized as a disease process triggered by a range of events. These triggers could include acute trauma, irregular or repetitive overload of joint structures, or aging-related spontaneous development.

Osteoarthritis’ Pathogenesis

  • The study highlights that the understanding of OA’s pathogenesis is continually evolving. It is increasingly viewed as a multifactorial condition in which the innate immune system assumes a crucial role. This system helps regulate and maintain low-grade inflammation, consequently causing persistent cartilage damage and disintegration.

Role of Innate Immunity in Osteoarthritis

  • The central role of the innate immune system in OA’s overall pathogenesis is critically examined in the paper. Macrophages, specific types of immune cells, that exist in the synovial fluid and synovium are identified as key regulators of immune processes in OA.
  • In responding to local and systemic cues, these macrophages can both trigger and subdue joint inflammation, thereby influencing the progression and severity of OA.
  • This comprehensive view on the influence of the immune system on OA is derived from a diverse set of perspectives encompassing humans studies, animal model studies, and other clinical and research investigations conducted on horses.

Therapeutic Management of Osteoarthritis

  • The paper also discusses the diverse immune modulatory therapeutic options currently available for managing OA. These treatment pathways can influence the immune factors that contribute to the disease, thereby potentially slowing its progression or reducing its symptoms.
  • Each therapeutic option’s mechanism of action is discussed laying the groundwork for selecting the most suitable treatment approach for different OA cases.

Cite This Article

APA
Estrada McDermott J, Pezzanite L, Goodrich L, Santangelo K, Chow L, Dow S, Wheat W. (2021). Role of Innate Immunity in Initiation and Progression of Osteoarthritis, with Emphasis on Horses. Animals (Basel), 11(11), 3247. https://doi.org/10.3390/ani11113247

Publication

Animals : an open access journal from MDPI
ISSN: 2076-2615
NlmUniqueID: 101635614
Country: Switzerland
Language: English
Volume: 11
Issue: 11
PII: 3247

Researcher Affiliations

Estrada McDermott, Juan
  • Department of Clinical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
Pezzanite, Lynn
  • Department of Clinical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
Goodrich, Laurie
  • Department of Clinical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
Santangelo, Kelly
  • Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523, USA.
Chow, Lyndah
  • Department of Clinical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
Dow, Steven
  • Department of Clinical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
  • Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523, USA.
Wheat, William
  • Department of Clinical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
  • Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523, USA.

Grant Funding

  • N/A / Fulbright Scholar Program
  • NCATS CTSA 5TL1TR002533-02 / NIH HHS
  • 5T32 OD010437 / NIH HHS
  • N/A / Carolyn Quan and Porter Bennett

Conflict of Interest Statement

The co-authors declare commercial affiliations with Validus Cellular Therapeutics (S.D. co-founder) and Advanced Regenerative Therapies (L.G. shareholder).

References

This article includes 101 references
  1. van Weeren PR, de Grauw JC. Pain in osteoarthritis.. Vet Clin North Am Equine Pract 2010 Dec;26(3):619-42.
    doi: 10.1016/j.cveq.2010.07.007pubmed: 21056303google scholar: lookup
  2. Sutton S, Clutterbuck A, Harris P, Gent T, Freeman S, Foster N, Barrett-Jolley R, Mobasheri A. The contribution of the synovium, synovial derived inflammatory cytokines and neuropeptides to the pathogenesis of osteoarthritis.. Vet J 2009 Jan;179(1):10-24.
    doi: 10.1016/j.tvjl.2007.08.013pubmed: 17911037google scholar: lookup
  3. Cisternas MG, Murphy L, Sacks JJ, Solomon DH, Pasta DJ, Helmick CG. Alternative Methods for Defining Osteoarthritis and the Impact on Estimating Prevalence in a US Population-Based Survey.. Arthritis Care Res (Hoboken) 2016 May;68(5):574-80.
    doi: 10.1002/acr.22721pmc: PMC4769961pubmed: 26315529google scholar: lookup
  4. Goodrich LR, Nixon AJ. Medical treatment of osteoarthritis in the horse - a review.. Vet J 2006 Jan;171(1):51-69.
    doi: 10.1016/j.tvjl.2004.07.008pubmed: 16427582google scholar: lookup
  5. Oke SL, McIlwraith CW. Review of the economic impact of osteoarthritis and oral joint-health supplements in horses.. Am. Assoc. Eq. Pract. 2010;10:12–16.
  6. Bogers SH. Cell-Based Therapies for Joint Disease in Veterinary Medicine: What We Have Learned and What We Need to Know.. Front Vet Sci 2018;5:70.
    doi: 10.3389/fvets.2018.00070pmc: PMC5911772pubmed: 29713634google scholar: lookup
  7. Ribitsch I, Oreff GL, Jenner F. Regenerative Medicine for Equine Musculoskeletal Diseases.. Animals (Basel) 2021 Jan 19;11(1).
    doi: 10.3390/ani11010234pmc: PMC7832834pubmed: 33477808google scholar: lookup
  8. Lories RJ, Luyten FP. Osteoarthritis, a disease bridging development and regeneration.. Bonekey Rep 2012;1:136.
    doi: 10.1038/bonekey.2012.136pmc: PMC3727791pubmed: 23951516google scholar: lookup
  9. Wu CL, Harasymowicz NS, Klimak MA, Collins KH, Guilak F. The role of macrophages in osteoarthritis and cartilage repair.. Osteoarthritis Cartilage 2020 May;28(5):544-554.
    doi: 10.1016/j.joca.2019.12.007pmc: PMC7214213pubmed: 31926267google scholar: lookup
  10. McIlwraith CW. Traumatic Arthritis and Post-Traumatic Osteoarthritis.. In: McIlwraith C.W., Frisbie D., Kawcak C., van Weeren R., editors. Joint Disease in the Horse. 2nd ed. Elsevier; St. Louis, MO, USA: Amsterdam, The Netherlands: 2016. pp. 33–48.
  11. Frisbie DD, Johnson SA. Synovial joint biology and pathobiology.. In: Auer J., Stick J., editors. Equine Surgery. Elsevier; Amsterdam, The Netherlands: 2018. pp. 1326–1348.
  12. Di Nicola V. Degenerative osteoarthritis a reversible chronic disease.. Regen Ther 2020 Dec;15:149-160.
    doi: 10.1016/j.reth.2020.07.007pmc: PMC7770340pubmed: 33426213google scholar: lookup
  13. Rinnovati R, Bonelli F, Tognetti R, Gallo C. Effect of Repeated Arthrocentesis on Cytology of Synovial Fluid.. J. Equine Vet. Sci. 2017;57:112–115.
    doi: 10.1016/j.jevs.2017.07.008google scholar: lookup
  14. Pauli C, Grogan SP, Patil S, Otsuki S, Hasegawa A, Koziol J, Lotz MK, D'Lima DD. Macroscopic and histopathologic analysis of human knee menisci in aging and osteoarthritis.. Osteoarthritis Cartilage 2011 Sep;19(9):1132-41.
    doi: 10.1016/j.joca.2011.05.008pmc: PMC3217905pubmed: 21683797google scholar: lookup
  15. Sellam J, Berenbaum F. The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis.. Nat Rev Rheumatol 2010 Nov;6(11):625-35.
    doi: 10.1038/nrrheum.2010.159pubmed: 20924410google scholar: lookup
  16. Bondeson J, Wainwright SD, Lauder S, Amos N, Hughes CE. The role of synovial macrophages and macrophage-produced cytokines in driving aggrecanases, matrix metalloproteinases, and other destructive and inflammatory responses in osteoarthritis.. Arthritis Res Ther 2006;8(6):R187.
    doi: 10.1186/ar2099pmc: PMC1794533pubmed: 17177994google scholar: lookup
  17. Dean G, Hoyland JA, Denton J, Donn RP, Freemont AJ. Mast cells in the synovium and synovial fluid in osteoarthritis.. Br J Rheumatol 1993 Aug;32(8):671-5.
    doi: 10.1093/rheumatology/32.8.671pubmed: 8348268google scholar: lookup
  18. Steel CM. Equine synovial fluid analysis.. Vet Clin North Am Equine Pract 2008 Aug;24(2):437-54, viii.
    doi: 10.1016/j.cveq.2008.05.004pubmed: 18652964google scholar: lookup
  19. Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors.. Nat Immunol 2010 May;11(5):373-84.
    doi: 10.1038/ni.1863pubmed: 20404851google scholar: lookup
  20. Cao SS, Kaufman RJ. Unfolded protein response.. Curr Biol 2012 Aug 21;22(16):R622-6.
    doi: 10.1016/j.cub.2012.07.004pubmed: 22917505google scholar: lookup
  21. Bergsbaken T, Fink SL, Cookson BT. Pyroptosis: host cell death and inflammation.. Nat Rev Microbiol 2009 Feb;7(2):99-109.
    doi: 10.1038/nrmicro2070pmc: PMC2910423pubmed: 19148178google scholar: lookup
  22. Okamura Y, Watari M, Jerud ES, Young DW, Ishizaka ST, Rose J, Chow JC, Strauss JF 3rd. The extra domain A of fibronectin activates Toll-like receptor 4.. J Biol Chem 2001 Mar 30;276(13):10229-33.
    doi: 10.1074/jbc.M100099200pubmed: 11150311google scholar: lookup
  23. Termeer C, Benedix F, Sleeman J, Fieber C, Voith U, Ahrens T, Miyake K, Freudenberg M, Galanos C, Simon JC. Oligosaccharides of Hyaluronan activate dendritic cells via toll-like receptor 4.. J Exp Med 2002 Jan 7;195(1):99-111.
    doi: 10.1084/jem.20001858pmc: PMC2196009pubmed: 11781369google scholar: lookup
  24. Sohn DH, Sokolove J, Sharpe O, Erhart JC, Chandra PE, Lahey LJ, Lindstrom TM, Hwang I, Boyer KA, Andriacchi TP, Robinson WH. Plasma proteins present in osteoarthritic synovial fluid can stimulate cytokine production via Toll-like receptor 4.. Arthritis Res Ther 2012 Jan 8;14(1):R7.
    doi: 10.1186/ar3555pmc: PMC3392793pubmed: 22225630google scholar: lookup
  25. Chen Y, Jiang W, Yong H, He M, Yang Y, Deng Z, Li Y. Macrophages in osteoarthritis: pathophysiology and therapeutics.. Am J Transl Res 2020;12(1):261-268.
    pmc: PMC7013211pubmed: 32051751
  26. Menarim BC, Gillis KH, Oliver A, Mason C, Ngo Y, Werre SR, Barrett SH, Luo X, Byron CR, Dahlgren LA. Autologous bone marrow mononuclear cells modulate joint homeostasis in an equine in vivo model of synovitis.. FASEB J 2019 Dec;33(12):14337-14353.
    doi: 10.1096/fj.201901684RRpubmed: 31665925google scholar: lookup
  27. Hawkins DL, MacKay RJ, MacKay SL, Moldawer LL. Human interleukin 10 suppresses production of inflammatory mediators by LPS-stimulated equine peritoneal macrophages.. Vet Immunol Immunopathol 1998 Nov 6;66(1):1-10.
    doi: 10.1016/S0165-2427(98)00181-0pubmed: 9847016google scholar: lookup
  28. Karagianni AE, Kapetanovic R, McGorum BC, Hume DA, Pirie SR. The equine alveolar macrophage: functional and phenotypic comparisons with peritoneal macrophages.. Vet Immunol Immunopathol 2013 Oct 1;155(4):219-28.
    doi: 10.1016/j.vetimm.2013.07.003pmc: PMC3795452pubmed: 23978307google scholar: lookup
  29. Wilson ME, McCandless EE, Olszewski MA, Robinson NE. Alveolar macrophage phenotypes in severe equine asthma.. Vet J 2020 Feb;256:105436.
    doi: 10.1016/j.tvjl.2020.105436pmc: PMC7768773pubmed: 32113585google scholar: lookup
  30. Murray PJ, Wynn TA. Protective and pathogenic functions of macrophage subsets.. Nat Rev Immunol 2011 Oct 14;11(11):723-37.
    doi: 10.1038/nri3073pmc: PMC3422549pubmed: 21997792google scholar: lookup
  31. Yang DH, Yang MY. The Role of Macrophage in the Pathogenesis of Osteoporosis.. Int J Mol Sci 2019 Apr 28;20(9).
    doi: 10.3390/ijms20092093pmc: PMC6539137pubmed: 31035384google scholar: lookup
  32. Murray PJ. Macrophage Polarization.. Annu Rev Physiol 2017 Feb 10;79:541-566.
    doi: 10.1146/annurev-physiol-022516-034339pubmed: 27813830google scholar: lookup
  33. Sommerfeld SD, Cherry C, Schwab RM, Chung L, Maestas DR, Laffont P, Stein J, Tam A, Housseau F, Taube J. Single cell RNA-seq in regenerative and fibrotic biomaterial environments defines new macrophage subsets.. Sci. Immunol. 2019:642389.
    doi: 10.1126/sciimunol.aax4783google scholar: lookup
  34. Yoshimoto T. The Hunt for the Source of Primary Interleukin-4: How We Discovered That Natural Killer T Cells and Basophils Determine T Helper Type 2 Cell Differentiation In Vivo.. Front Immunol 2018;9:716.
    doi: 10.3389/fimmu.2018.00716pmc: PMC5924770pubmed: 29740428google scholar: lookup
  35. Dey A, Allen J, Hankey-Giblin PA. Ontogeny and polarization of macrophages in inflammation: blood monocytes versus tissue macrophages.. Front Immunol 2014;5:683.
    doi: 10.3389/fimmu.2014.00683pmc: PMC4303141pubmed: 25657646google scholar: lookup
  36. Murray PJ, Allen JE, Biswas SK, Fisher EA, Gilroy DW, Goerdt S, Gordon S, Hamilton JA, Ivashkiv LB, Lawrence T, Locati M, Mantovani A, Martinez FO, Mege JL, Mosser DM, Natoli G, Saeij JP, Schultze JL, Shirey KA, Sica A, Suttles J, Udalova I, van Ginderachter JA, Vogel SN, Wynn TA. Macrophage activation and polarization: nomenclature and experimental guidelines.. Immunity 2014 Jul 17;41(1):14-20.
    doi: 10.1016/j.immuni.2014.06.008pmc: PMC4123412pubmed: 25035950google scholar: lookup
  37. Duan L, Mukherjee E. Janeway’s Immunobiology, Ninth Edition.. Yale J. Biol. Med. 2016;89:424–425.
  38. van den Bosch MHJ, van Lent PLEM, van der Kraan PM. Identifying effector molecules, cells, and cytokines of innate immunity in OA.. Osteoarthritis Cartilage 2020 May;28(5):532-543.
    doi: 10.1016/j.joca.2020.01.016pubmed: 32044352google scholar: lookup
  39. Griffin TM, Lories RJ. Cracking the code on the innate immune program in OA.. Osteoarthritis Cartilage 2020 May;28(5):529-531.
    doi: 10.1016/j.joca.2020.03.013pubmed: 32278072google scholar: lookup
  40. Menarim BC, Gillis KH, Oliver A, Mason C, Werre SR, Luo X, Byron CR, Kalbfleisch TS, MacLeod JN, Dahlgren LA. Inflamed synovial fluid induces a homeostatic response in bone marrow mononuclear cells in vitro: Implications for joint therapy.. FASEB J 2020 Mar;34(3):4430-4444.
    doi: 10.1096/fj.201902698Rpubmed: 32030831google scholar: lookup
  41. Bullone M, Lavoie JP. The Contribution of Oxidative Stress and Inflamm-Aging in Human and Equine Asthma.. Int J Mol Sci 2017 Dec 5;18(12).
    doi: 10.3390/ijms18122612pmc: PMC5751215pubmed: 29206130google scholar: lookup
  42. Karagianni AE, Kapetanovic R, Summers KM, McGorum BC, Hume DA, Pirie RS. Comparative transcriptome analysis of equine alveolar macrophages.. Equine Vet J 2017 May;49(3):375-382.
    doi: 10.1111/evj.12584pmc: PMC5412682pubmed: 27096353google scholar: lookup
  43. Ross TN, Kisiday JD, Hess T, McIlwraith CW. Evaluation of the inflammatory response in experimentally induced synovitis in the horse: a comparison of recombinant equine interleukin 1 beta and lipopolysaccharide.. Osteoarthritis Cartilage 2012 Dec;20(12):1583-90.
    doi: 10.1016/j.joca.2012.08.008pubmed: 22917743google scholar: lookup
  44. Hammond RA, Hannon R, Frean SP, Armstrong SJ, Flower RJ, Bryant CE. Endotoxin induction of nitric oxide synthase and cyclooxygenase-2 in equine alveolar macrophages.. Am J Vet Res 1999 Apr;60(4):426-31.
    pubmed: 10211684
  45. Moore BD, Balasuriya UB, Watson JL, Bosio CM, MacKay RJ, MacLachlan NJ. Virulent and avirulent strains of equine arteritis virus induce different quantities of TNF-alpha and other proinflammatory cytokines in alveolar and blood-derived equine macrophages.. Virology 2003 Sep 30;314(2):662-70.
    doi: 10.1016/S0042-6822(03)00506-3pubmed: 14554093google scholar: lookup
  46. So A, Busso N. The concept of the inflammasome and its rheumatologic implications.. Joint Bone Spine 2014 Oct;81(5):398-402.
    pubmed: 24703401doi: 10.1016/j.jbspin.2014.02.009google scholar: lookup
  47. Netea MG, Nold-Petry CA, Nold MF, Joosten LA, Opitz B, van der Meer JH, van de Veerdonk FL, Ferwerda G, Heinhuis B, Devesa I, Funk CJ, Mason RJ, Kullberg BJ, Rubartelli A, van der Meer JW, Dinarello CA. Differential requirement for the activation of the inflammasome for processing and release of IL-1beta in monocytes and macrophages.. Blood 2009 Mar 5;113(10):2324-35.
    doi: 10.1182/blood-2008-03-146720pmc: PMC2652374pubmed: 19104081google scholar: lookup
  48. Chen Z, Zhong H, Wei J, Lin S, Zong Z, Gong F, Huang X, Sun J, Li P, Lin H, Wei B, Chu J. Inhibition of Nrf2/HO-1 signaling leads to increased activation of the NLRP3 inflammasome in osteoarthritis.. Arthritis Res Ther 2019 Dec 23;21(1):300.
    doi: 10.1186/s13075-019-2085-6pmc: PMC6929452pubmed: 31870428google scholar: lookup
  49. Ahn H, Kim J, Lee H, Lee E, Lee GS. Characterization of equine inflammasomes and their regulation.. Vet Res Commun 2020 May;44(2):51-59.
    doi: 10.1007/s11259-020-09772-1pubmed: 32297137google scholar: lookup
  50. Hennig P, Garstkiewicz M, Grossi S, Di Filippo M, French LE, Beer HD. The Crosstalk between Nrf2 and Inflammasomes.. Int J Mol Sci 2018 Feb 13;19(2).
    doi: 10.3390/ijms19020562pmc: PMC5855784pubmed: 29438305google scholar: lookup
  51. van der Kraan PM. Factors that influence outcome in experimental osteoarthritis.. Osteoarthritis Cartilage 2017 Mar;25(3):369-375.
    doi: 10.1016/j.joca.2016.09.005pubmed: 27616682google scholar: lookup
  52. Samvelyan HJ, Hughes D, Stevens C, Staines KA. Models of Osteoarthritis: Relevance and New Insights.. Calcif Tissue Int 2021 Sep;109(3):243-256.
    doi: 10.1007/s00223-020-00670-xpmc: PMC8403120pubmed: 32062692google scholar: lookup
  53. Seok J, Warren HS, Cuenca AG, Mindrinos MN, Baker HV, Xu W, Richards DR, McDonald-Smith GP, Gao H, Hennessy L, Finnerty CC, López CM, Honari S, Moore EE, Minei JP, Cuschieri J, Bankey PE, Johnson JL, Sperry J, Nathens AB, Billiar TR, West MA, Jeschke MG, Klein MB, Gamelli RL, Gibran NS, Brownstein BH, Miller-Graziano C, Calvano SE, Mason PH, Cobb JP, Rahme LG, Lowry SF, Maier RV, Moldawer LL, Herndon DN, Davis RW, Xiao W, Tompkins RG. Genomic responses in mouse models poorly mimic human inflammatory diseases.. Proc Natl Acad Sci U S A 2013 Feb 26;110(9):3507-12.
    doi: 10.1073/pnas.1222878110pmc: PMC3587220pubmed: 23401516google scholar: lookup
  54. Frisbie DD, Cross MW, McIlwraith CW. A comparative study of articular cartilage thickness in the stifle of animal species used in human pre-clinical studies compared to articular cartilage thickness in the human knee.. Vet Comp Orthop Traumatol 2006;19(3):142-6.
    doi: 10.1055/s-0038-1632990pubmed: 16971996google scholar: lookup
  55. McIlwraith CW, Frisbie DD, Kawcak CE. The horse as a model of naturally occurring osteoarthritis.. Bone Joint Res 2012 Nov;1(11):297-309.
    doi: 10.1302/2046-3758.111.2000132pmc: PMC3626203pubmed: 23610661google scholar: lookup
  56. Colbath AC, Frisbie DD, Dow SW, Kisiday JD, McIlwraith CW, Goodrich LR. Equine Models for the Investigation of Mesenchymal Stem Cell Therapies in Orthopaedic Disease.. Oper. Tech. Sports Med. 2017;25:41–49.
    doi: 10.1053/j.otsm.2016.12.007google scholar: lookup
  57. Barrachina L, Cequier A, Romero A, Vitoria A, Zaragoza P, Vázquez FJ, Rodellar C. Allo-antibody production after intraarticular administration of mesenchymal stem cells (MSCs) in an equine osteoarthritis model: effect of repeated administration, MSC inflammatory stimulation, and equine leukocyte antigen (ELA) compatibility.. Stem Cell Res Ther 2020 Feb 7;11(1):52.
    doi: 10.1186/s13287-020-1571-8pmc: PMC7006079pubmed: 32028995google scholar: lookup
  58. Miller RJ, Malfait AM, Miller RE. The innate immune response as a mediator of osteoarthritis pain.. Osteoarthritis Cartilage 2020 May;28(5):562-571.
    doi: 10.1016/j.joca.2019.11.006pmc: PMC6951330pubmed: 31862470google scholar: lookup
  59. Miao H, Chen L, Hao L, Zhang X, Chen Y, Ruan Z, Liang H. Stearic acid induces proinflammatory cytokine production partly through activation of lactate-HIF1α pathway in chondrocytes.. Sci Rep 2015 Aug 14;5:13092.
    doi: 10.1038/srep13092pmc: PMC4536527pubmed: 26271607google scholar: lookup
  60. Chevalier X, Eymard F, Richette P. Biologic agents in osteoarthritis: hopes and disappointments.. Nat Rev Rheumatol 2013 Jul;9(7):400-10.
    doi: 10.1038/nrrheum.2013.44pubmed: 23545735google scholar: lookup
  61. Yuan XL, Meng HY, Wang YC, Peng J, Guo QY, Wang AY, Lu SB. Bone-cartilage interface crosstalk in osteoarthritis: potential pathways and future therapeutic strategies.. Osteoarthritis Cartilage 2014 Aug;22(8):1077-89.
    doi: 10.1016/j.joca.2014.05.023pubmed: 24928319google scholar: lookup
  62. Schnabel LV, Fortier LA, McIlwraith CW, Nobert KM. Therapeutic use of stem cells in horses: which type, how, and when?. Vet J 2013 Sep;197(3):570-7.
    doi: 10.1016/j.tvjl.2013.04.018pubmed: 23778257google scholar: lookup
  63. Colbath AC, Dow SW, Phillips JN, McIlwraith CW, Goodrich LR. Autologous and Allogeneic Equine Mesenchymal Stem Cells Exhibit Equivalent Immunomodulatory Properties In Vitro.. Stem Cells Dev 2017 Apr 1;26(7):503-511.
    doi: 10.1089/scd.2016.0266pubmed: 27958776google scholar: lookup
  64. Lombana KG, Goodrich LR, Phillips JN, Kisiday JD, Ruple-Czerniak A, McIlwraith CW. An Investigation of Equine Mesenchymal Stem Cell Characteristics from Different Harvest Sites: More Similar Than Not.. Front Vet Sci 2015;2:67.
    doi: 10.3389/fvets.2015.00067pmc: PMC4672231pubmed: 26664993google scholar: lookup
  65. Carrade Holt DD, Wood JA, Granick JL, Walker NJ, Clark KC, Borjesson DL. Equine mesenchymal stem cells inhibit T cell proliferation through different mechanisms depending on tissue source.. Stem Cells Dev 2014 Jun 1;23(11):1258-65.
    doi: 10.1089/scd.2013.0537pubmed: 24438346google scholar: lookup
  66. Kyurkchiev D, Bochev I, Ivanova-Todorova E, Mourdjeva M, Oreshkova T, Belemezova K, Kyurkchiev S. Secretion of immunoregulatory cytokines by mesenchymal stem cells.. World J Stem Cells 2014 Nov 26;6(5):552-70.
    doi: 10.4252/wjsc.v6.i5.552pmc: PMC4178255pubmed: 25426252google scholar: lookup
  67. Castro-Manrreza ME, Montesinos JJ. Immunoregulation by mesenchymal stem cells: biological aspects and clinical applications.. J Immunol Res 2015;2015:394917.
    doi: 10.1155/2015/394917pmc: PMC4417567pubmed: 25961059google scholar: lookup
  68. Shen PC, Wu CL, Jou IM, Lee CH, Juan HY, Lee PJ, Chen SH, Hsieh JL. T helper cells promote disease progression of osteoarthritis by inducing macrophage inflammatory protein-1γ.. Osteoarthritis Cartilage 2011 Jun;19(6):728-36.
    doi: 10.1016/j.joca.2011.02.014pubmed: 21376128google scholar: lookup
  69. Nees TA, Rosshirt N, Zhang JA, Platzer H, Sorbi R, Tripel E, Reiner T, Walker T, Schiltenwolf M, Lorenz HM, Tretter T, Moradi B, Hagmann S. T Helper Cell Infiltration in Osteoarthritis-Related Knee Pain and Disability.. J Clin Med 2020 Jul 29;9(8).
    doi: 10.3390/jcm9082423pmc: PMC7464429pubmed: 32751139google scholar: lookup
  70. Glennie S, Soeiro I, Dyson PJ, Lam EW, Dazzi F. Bone marrow mesenchymal stem cells induce division arrest anergy of activated T cells.. Blood 2005 Apr 1;105(7):2821-7.
    doi: 10.1182/blood-2004-09-3696pubmed: 15591115google scholar: lookup
  71. Plumas J, Chaperot L, Richard MJ, Molens JP, Bensa JC, Favrot MC. Mesenchymal stem cells induce apoptosis of activated T cells.. Leukemia 2005 Sep;19(9):1597-604.
    doi: 10.1038/sj.leu.2403871pubmed: 16049516google scholar: lookup
  72. Negi N, Griffin MD. Effects of mesenchymal stromal cells on regulatory T cells: Current understanding and clinical relevance.. Stem Cells 2020 May;38(5):596-605.
    doi: 10.1002/stem.3151pmc: PMC7217190pubmed: 31995249google scholar: lookup
  73. Azevedo RI, Minskaia E, Fernandes-Platzgummer A, Vieira AIS, da Silva CL, Cabral JMS, Lacerda JF. Mesenchymal stromal cells induce regulatory T cells via epigenetic conversion of human conventional CD4 T cells in vitro.. Stem Cells 2020 Aug;38(8):1007-1019.
    doi: 10.1002/stem.3185pmc: PMC7497276pubmed: 32352186google scholar: lookup
  74. Mancuso P, Raman S, Glynn A, Barry F, Murphy JM. Mesenchymal stem cell therapy modulates synovial macrophages in a murine model of osteoarthritis.. Osteoarthr. Cartilage. 2019;7:9.
    doi: 10.1016/j.joca.2019.02.440google scholar: lookup
  75. Cassano JM, Schnabel LV, Goodale MB, Fortier LA. Inflammatory licensed equine MSCs are chondroprotective and exhibit enhanced immunomodulation in an inflammatory environment.. Stem Cell Res Ther 2018 Apr 3;9(1):82.
    doi: 10.1186/s13287-018-0840-2pmc: PMC5883371pubmed: 29615127google scholar: lookup
  76. Barrachina L, Remacha AR, Romero A, Vázquez FJ, Albareda J, Prades M, Gosálvez J, Roy R, Zaragoza P, Martín-Burriel I, Rodellar C. Priming Equine Bone Marrow-Derived Mesenchymal Stem Cells with Proinflammatory Cytokines: Implications in Immunomodulation-Immunogenicity Balance, Cell Viability, and Differentiation Potential.. Stem Cells Dev 2017 Jan 1;26(1):15-24.
    doi: 10.1089/scd.2016.0209pubmed: 27712399google scholar: lookup
  77. Whitworth DJ, Banks TA. Stem cell therapies for treating osteoarthritis: prescient or premature?. Vet J 2014 Dec;202(3):416-24.
    doi: 10.1016/j.tvjl.2014.09.024pubmed: 25457267google scholar: lookup
  78. Goodrich LR, Chen AC, Werpy NM, Williams AA, Kisiday JD, Su AW, Cory E, Morley PS, McIlwraith CW, Sah RL, Chu CR. Addition of Mesenchymal Stem Cells to Autologous Platelet-Enhanced Fibrin Scaffolds in Chondral Defects: Does It Enhance Repair?. J Bone Joint Surg Am 2016 Jan 6;98(1):23-34.
    doi: 10.2106/JBJS.O.00407pmc: PMC4697360pubmed: 26738900google scholar: lookup
  79. Broeckx SY, Martens AM, Bertone AL, Van Brantegem L, Duchateau L, Van Hecke L, Dumoulin M, Oosterlinck M, Chiers K, Hussein H, Pille F, Spaas JH. The use of equine chondrogenic-induced mesenchymal stem cells as a treatment for osteoarthritis: A randomised, double-blinded, placebo-controlled proof-of-concept study.. Equine Vet J 2019 Nov;51(6):787-794.
    doi: 10.1111/evj.13089pmc: PMC6850029pubmed: 30815897google scholar: lookup
  80. Klymiuk MC, Balz N, Elashry MI, Heimann M, Wenisch S, Arnhold S. Exosomes isolation and identification from equine mesenchymal stem cells.. BMC Vet Res 2019 Jan 28;15(1):42.
    doi: 10.1186/s12917-019-1789-9pmc: PMC6348641pubmed: 30691449google scholar: lookup
  81. Oh JY, Kim MK, Shin MS, Lee HJ, Ko JH, Wee WR, Lee JH. The anti-inflammatory and anti-angiogenic role of mesenchymal stem cells in corneal wound healing following chemical injury.. Stem Cells 2008 Apr;26(4):1047-55.
    doi: 10.1634/stemcells.2007-0737pubmed: 18192235google scholar: lookup
  82. Ziegler A, Everett H, Hamza E, Garbani M, Gerber V, Marti E, Steinbach F. Equine dendritic cells generated with horse serum have enhanced functionality in comparison to dendritic cells generated with fetal bovine serum.. BMC Vet Res 2016 Nov 15;12(1):254.
    doi: 10.1186/s12917-016-0880-8pmc: PMC5111218pubmed: 27846835google scholar: lookup
  83. Garbin LC, Olver CS. Platelet-Rich Products and Their Application to Osteoarthritis.. J Equine Vet Sci 2020 Mar;86:102820.
    doi: 10.1016/j.jevs.2019.102820pubmed: 32067662google scholar: lookup
  84. Dregalla RC, Herrera JA, Donner EJ. Soluble factors differ in platelets derived from separate niches: a pilot study comparing the secretome of peripheral blood and bone marrow platelets.. Cytotherapy 2021 Aug;23(8):677-682.
    doi: 10.1016/j.jcyt.2021.01.004pubmed: 33678599google scholar: lookup
  85. Belk JW, Kraeutler MJ, Houck DA, Goodrich JA, Dragoo JL, McCarty EC. Platelet-Rich Plasma Versus Hyaluronic Acid for Knee Osteoarthritis: A Systematic Review and Meta-analysis of Randomized Controlled Trials.. Am J Sports Med 2021 Jan;49(1):249-260.
    doi: 10.1177/0363546520909397pubmed: 32302218google scholar: lookup
  86. Nelson BB, Goodrich LR. Treatment of Joint Disease.. In: Sprayberry K.A., Robinson N.E., editors. Robinson’s Current Therapy in Equine Medicine. 7th ed. W.B. Saunders; St. Louis, MO, USA: 2015. pp. 798–804.
  87. Wanstrath AW, Hettlich BF, Su L, Smith A, Zekas LJ, Allen MJ, Bertone AL. Evaluation of a Single Intra-Articular Injection of Autologous Protein Solution for Treatment of Osteoarthritis in a Canine Population.. Vet Surg 2016 Aug;45(6):764-74.
    doi: 10.1111/vsu.12512pubmed: 27391909google scholar: lookup
  88. Fahy N, de Vries-van Melle ML, Lehmann J, Wei W, Grotenhuis N, Farrell E, van der Kraan PM, Murphy JM, Bastiaansen-Jenniskens YM, van Osch GJ. Human osteoarthritic synovium impacts chondrogenic differentiation of mesenchymal stem cells via macrophage polarisation state.. Osteoarthritis Cartilage 2014 Aug;22(8):1167-75.
    doi: 10.1016/j.joca.2014.05.021pubmed: 24911520google scholar: lookup
  89. Menarim BC, Gillis KH, Oliver A, Ngo Y, Werre SR, Barrett SH, Rodgerson DH, Dahlgren LA. Macrophage Activation in the Synovium of Healthy and Osteoarthritic Equine Joints.. Front Vet Sci 2020;7:568756.
    doi: 10.21203/rs.3.rs-19784/v1pmc: PMC7726135pubmed: 33324696google scholar: lookup
  90. Lu X, Li N, Zhao L, Guo D, Yi H, Yang L, Liu X, Sun D, Nian H, Wei R. Human umbilical cord mesenchymal stem cells alleviate ongoing autoimmune dacryoadenitis in rabbits via polarizing macrophages into an anti-inflammatory phenotype.. Exp Eye Res 2020 Feb;191:107905.
    doi: 10.1016/j.exer.2019.107905pmc: PMC8612174pubmed: 31891674google scholar: lookup
  91. Pietras EM, Mirantes-Barbeito C, Fong S, Loeffler D, Kovtonyuk LV, Zhang S, Lakshminarasimhan R, Chin CP, Techner JM, Will B, Nerlov C, Steidl U, Manz MG, Schroeder T, Passegué E. Chronic interleukin-1 exposure drives haematopoietic stem cells towards precocious myeloid differentiation at the expense of self-renewal.. Nat Cell Biol 2016 Jun;18(6):607-18.
    doi: 10.1038/ncb3346pmc: PMC4884136pubmed: 27111842google scholar: lookup
  92. Goodrich LR, Grieger JC, Phillips JN, Khan N, Gray SJ, McIlwraith CW, Samulski RJ. scAAVIL-1ra dosing trial in a large animal model and validation of long-term expression with repeat administration for osteoarthritis therapy.. Gene Ther 2015 Jul;22(7):536-45.
    doi: 10.1038/gt.2015.21pmc: PMC5567794pubmed: 25902762google scholar: lookup
  93. Watson Levings RS, Broome TA, Smith AD, Rice BL, Gibbs EP, Myara DA, Hyddmark EV, Nasri E, Zarezadeh A, Levings PP, Lu Y, White ME, Dacanay EA, Foremny GB, Evans CH, Morton AJ, Winter M, Dark MJ, Nickerson DM, Colahan PT, Ghivizzani SC. Gene Therapy for Osteoarthritis: Pharmacokinetics of Intra-Articular Self-Complementary Adeno-Associated Virus Interleukin-1 Receptor Antagonist Delivery in an Equine Model.. Hum Gene Ther Clin Dev 2018 Jun;29(2):90-100.
    doi: 10.1089/humc.2017.142pmc: PMC6007808pubmed: 29869540google scholar: lookup
  94. De Souza MV. Osteoarthritis in horses—Part 2, A review of the intra-articular use of corticosteroids as a method of treatment.. Braz. Arch. Biol. Technol. 2016.
    doi: 10.1590/1678-4324-2016150025google scholar: lookup
  95. Hu Y, Chen X, Wang S, Jing Y, Su J. Subchondral bone microenvironment in osteoarthritis and pain.. Bone Res 2021 Mar 17;9(1):20.
    doi: 10.1038/s41413-021-00147-zpmc: PMC7969608pubmed: 33731688google scholar: lookup
  96. Chu CR, Fortier LA, Williams A, Payne KA, McCarrel TM, Bowers ME, Jaramillo D. Minimally Manipulated Bone Marrow Concentrate Compared with Microfracture Treatment of Full-Thickness Chondral Defects: A One-Year Study in an Equine Model.. J Bone Joint Surg Am 2018 Jan 17;100(2):138-146.
    doi: 10.2106/JBJS.17.00132pmc: PMC6819026pubmed: 29342064google scholar: lookup
  97. Pezzanite LM, Chow L, Johnson V, Griffenhagen GM, Goodrich L, Dow S. Toll-like receptor activation of equine mesenchymal stromal cells to enhance antibacterial activity and immunomodulatory cytokine secretion.. Vet Surg 2021 May;50(4):858-871.
    doi: 10.1111/vsu.13628pubmed: 33797775google scholar: lookup
  98. Chow L, Johnson V, Impastato R, Coy J, Strumpf A, Dow S. Antibacterial activity of human mesenchymal stem cells mediated directly by constitutively secreted factors and indirectly by activation of innate immune effector cells.. Stem Cells Transl Med 2020 Feb;9(2):235-249.
    doi: 10.1002/sctm.19-0092pmc: PMC6988770pubmed: 31702119google scholar: lookup
  99. Johnson V, Webb T, Norman A, Coy J, Kurihara J, Regan D, Dow S. Activated Mesenchymal Stem Cells Interact with Antibiotics and Host Innate Immune Responses to Control Chronic Bacterial Infections.. Sci Rep 2017 Aug 29;7(1):9575.
    doi: 10.1038/s41598-017-08311-4pmc: PMC5575141pubmed: 28851894google scholar: lookup
  100. Culemann S, Grüneboom A, Nicolás-Ávila JÁ, Weidner D, Lämmle KF, Rothe T, Quintana JA, Kirchner P, Krljanac B, Eberhardt M, Ferrazzi F, Kretzschmar E, Schicht M, Fischer K, Gelse K, Faas M, Pfeifle R, Ackermann JA, Pachowsky M, Renner N, Simon D, Haseloff RF, Ekici AB, Bäuerle T, Blasig IE, Vera J, Voehringer D, Kleyer A, Paulsen F, Schett G, Hidalgo A, Krönke G. Locally renewing resident synovial macrophages provide a protective barrier for the joint.. Nature 2019 Aug;572(7771):670-675.
    doi: 10.1038/s41586-019-1471-1pmc: PMC6805223pubmed: 31391580google scholar: lookup
  101. Kurowska-Stolarska M, Alivernini S. Synovial tissue macrophages: friend or foe?. RMD Open 2017;3(2):e000527.
    doi: 10.1136/rmdopen-2017-000527pmc: PMC5729306pubmed: 29299338google scholar: lookup

Citations

This article has been cited 12 times.
  1. Wang GS, Lee KT, Lin SL, Hou SM, Fong YC, Tang CH, Lin CY. WISP-3 facilitates CCL4-dependent monocyte migration and M1 polarization in rheumatoid arthritis by inhibiting miR-6894-5p. Int J Med Sci 2026;23(1):301-312.
    doi: 10.7150/ijms.122642pubmed: 41399379google scholar: lookup
  2. Asahi Y, Arai T, Tanaka Y. Changes in plasma metabolite concentrations and enzyme activities in aging riding horses. Front Vet Sci 2024;11:1345548.
    doi: 10.3389/fvets.2024.1345548pubmed: 38881783google scholar: lookup
  3. Chen B, Sun Y, Xu G, Jiang J, Zhang W, Wu C, Xue P, Cui Z. Role of crosstalk between synovial cells and chondrocytes in osteoarthritis (Review). Exp Ther Med 2024 May;27(5):201.
    doi: 10.3892/etm.2024.12490pubmed: 38590580google scholar: lookup
  4. Ko CY, Lin YY, Achudhan D, Chang JW, Liu SC, Lai CY, Huang YL, Tsai CH, Fong YC, Chen HT, Lee KT, Huang CC, Chang TK, Tang CH. Omentin-1 ameliorates the progress of osteoarthritis by promoting IL-4-dependent anti-inflammatory responses and M2 macrophage polarization. Int J Biol Sci 2023;19(16):5275-5289.
    doi: 10.7150/ijbs.86701pubmed: 37928270google scholar: lookup
  5. O'Brien TJ, Hollinshead F, Goodrich LR. Extracellular vesicles in the treatment and prevention of osteoarthritis: can horses help us translate this therapy to humans?. Extracell Vesicles Circ Nucl Acids 2023 Jun;4(2):151-169.
    doi: 10.20517/evcna.2023.11pubmed: 37829144google scholar: lookup
  6. Thampi P, Seabaugh KA, Pezzanite LM, Chu CR, Phillips JN, Grieger JC, McIlwraith CW, Samulski RJ, Goodrich LR. A pilot study to determine the optimal dose of scAAVIL-1ra in a large animal model of post-traumatic osteoarthritis. Gene Ther 2023 Dec;30(12):792-800.
    doi: 10.1038/s41434-023-00420-2pubmed: 37696981google scholar: lookup
  7. Mayet A, Zablotski Y, Roth SP, Brehm W, Troillet A. Systematic review and meta-analysis of positive long-term effects after intra-articular administration of orthobiologic therapeutics in horses with naturally occurring osteoarthritis. Front Vet Sci 2023;10:1125695.
    doi: 10.3389/fvets.2023.1125695pubmed: 36908512google scholar: lookup
  8. Fine N, Lively S, Séguin CA, Perruccio AV, Kapoor M, Rampersaud R. Intervertebral disc degeneration and osteoarthritis: a common molecular disease spectrum. Nat Rev Rheumatol 2023 Mar;19(3):136-152.
    doi: 10.1038/s41584-022-00888-zpubmed: 36702892google scholar: lookup
  9. DeNotta S, McFarlane D. Immunosenescence and inflammaging in the aged horse. Immun Ageing 2023 Jan 6;20(1):2.
    doi: 10.1186/s12979-022-00325-5pubmed: 36609345google scholar: lookup
  10. Thampi P, Samulski RJ, Grieger JC, Phillips JN, McIlwraith CW, Goodrich LR. Gene therapy approaches for equine osteoarthritis. Front Vet Sci 2022;9:962898.
    doi: 10.3389/fvets.2022.962898pubmed: 36246316google scholar: lookup
  11. Soontararak S, Ardaum P, Senarat N, Yangtara S, Lekcharoensuk C, Putchong I, Kashemsant N, Vijarnsorn M, Chow L, Dow S, Lekcharoensuk P. In Vitro Anti-Inflammatory and Regenerative Effects of Autologous Conditioned Serum from Dogs with Osteoarthritis. Animals (Basel) 2022 Oct 10;12(19).
    doi: 10.3390/ani12192717pubmed: 36230458google scholar: lookup
  12. Gao S, Song H. Integrated comparison of the mRNAome in cartilage, synovium, and macrophages in osteoarthritis. Z Rheumatol 2024 Feb;83(Suppl 1):62-70.
    doi: 10.1007/s00393-022-01171-ypubmed: 35178608google scholar: lookup
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