FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / Front Vet Sci / Macrophage Activation in the Synovium of Healthy and Osteoar...
Frontiers in veterinary science2020; 7; 568756; doi: 10.3389/fvets.2020.568756

Macrophage Activation in the Synovium of Healthy and Osteoarthritic Equine Joints.

Abstract: Synovitis is a major component of osteoarthritis and is driven primarily by macrophages. Synovial macrophages are crucial for joint homeostasis (M2-like phenotype), but induce inflammation (M1-like) when regulatory functions become overwhelmed. Macrophage phenotypes in synovium from osteoarthritic and healthy joints are poorly characterized; however, comparative knowledge of their phenotypes during health and disease is paramount for developing targeted treatments. This study compared patterns of macrophage activation in healthy and osteoarthritic equine synovium and correlated histology with cytokine/chemokine profiles in synovial fluid. Synovial histology and immunohistochemistry for M1-like (CD86), M2-like (CD206, IL-10), and pan macrophage (CD14) markers were performed on biopsies from 29 healthy and 26 osteoarthritic equine joints. Synovial fluid cytokines (MCP-1, IL-10, PGE2, IL-1β, IL-6, TNF-α, IL-1ra) and growth factors (GM-CSF, SDF-1α+β, IGF-1, and FGF-2) were quantified. Macrophage phenotypes were not as clearly defined in vivo as they are in vitro. All macrophage markers were expressed with minimal differences between OA and normal joints. Expression for all markers increased proportionate to synovial inflammation, especially CD86. Synovial fluid MCP-1 was higher in osteoarthritic joints while SDF-1 and IL-10 were lower, and PGE2 concentrations did not differ between groups. Increased CD14/CD86/CD206/IL-10 expression was associated with synovial hyperplasia, consistent with macrophage recruitment and activation in response to injury. Lower synovial fluid IL-10 could suggest that homeostatic mechanisms from synovial macrophages became overwhelmed preventing inflammation resolution, resulting in chronic inflammation and OA. Further investigations into mechanisms of arthritis resolution are warranted. Developing pro-resolving therapies may provide superior results in the treatment of OA.
Copyright © 2020 Menarim, Gillis, Oliver, Ngo, Werre, Barrett, Rodgerson and Dahlgren.
Get Full Text
Publication Date: 2020-11-26 PubMed ID: 33324696PubMed Central: PMC7726135DOI: 10.3389/fvets.2020.568756Google 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.
LinkedInCopy
  • Journal Article

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 study investigates the role and activation patterns of synovial macrophages, critical for joint health, in osteoarthritic and healthy equine joints. Researchers found that in osteoarthritic conditions, synovial macrophages could fail to maintain homeostasis, implying the need for further investigation and development of targeted arthritis resolution therapies.

Macrophage Roles and Phenotypes

  • Macrophages are essential for maintaining joint health (represented by the M2-like phenotype).
  • However, when their regulatory functions are overwhelmed, they induce inflammation, represented by the M1-like phenotype.
  • This study provides comparative information on the macrophage phenotypes in healthy and diseased (osteoarthritic) joints, which is important for the development of targeted treatments.

Study Method and Findings

  • Biopsies were conducted on synovium from 29 healthy and 26 osteoarthritic equine joints, with researchers performing synovial histology and immunohistochemistry for M1-like (CD86), M2-like (CD206, IL-10), and pan macrophage (CD14) markers.
  • The study found that all macrophage markers were expressed with minimal differences being seen between osteoarthritic (OA) and normal joints, indicating that macrophage phenotypes were not as clearly defined as previously understood.
  • The expression for all markers increased proportionately to synovial inflammation, especially CD86.
  • Notably, a chemokine, MCP-1, were found in higher concentrations in the synovial fluid of osteoarthritic joints, while SDF-1 and IL-10 were lower, indicating potential correlation with the arthritis condition.
  • However, PGE concentrations were similar in both normal and OA joint samples, arguing against any differential role of PGE in these conditions.

Implications

  • Increased macrophage marker expression (CD14/CD86/CD206/IL-10) was linked to synovial hyperplasia. This finding suggests that macrophages are recruited and activated in response to injury.
  • The lower concentration of synovial fluid IL-10 in osteoarthritic joints indicates that the homeostatic mechanisms managed by synovial macrophages may become overwhelmed, preventing successful inflammation resolution.
  • This can lead to chronic inflammation and eventually to osteoarthritis.
  • These findings underline the need for further research into the mechanisms of arthritis resolution. The development of pro-resolving therapies may provide superior results in treating osteoarthritis, potentially offering more effective solutions than currently available treatments.

Cite This Article

APA
Menarim BC, Gillis KH, Oliver A, Ngo Y, Werre SR, Barrett SH, Rodgerson DH, Dahlgren LA. (2020). Macrophage Activation in the Synovium of Healthy and Osteoarthritic Equine Joints. Front Vet Sci, 7, 568756. https://doi.org/10.3389/fvets.2020.568756

Publication

Frontiers in veterinary science
ISSN: 2297-1769
NlmUniqueID: 101666658
Country: Switzerland
Language: English
Volume: 7
Pages: 568756

Researcher Affiliations

Menarim, Bruno C
  • Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States.
Gillis, Kiersten H
  • Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States.
Oliver, Andrea
  • Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States.
Ngo, Ying
  • Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States.
Werre, Stephen R
  • Laboratory for Study Design and Statistical Analysis, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States.
Barrett, Sarah H
  • Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States.
Rodgerson, Dwayne H
  • Hagyard Equine Medical Institute, Lexington, KY, United States.
Dahlgren, Linda A
  • Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States.

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

This article includes 113 references
  1. McIlwraith CW, Frisbie DD, Kawcak CE. The horse as a model of naturally occurring osteoarthritis.. Bone Joint Res (2012) 1:297–309.
    doi: 10.1302/2046-3758.111.2000132pmc: PMC3626203pubmed: 23610661google scholar: lookup
  2. 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 (2016) 68:574–80.
    doi: 10.1002/acr.22721pmc: PMC4769961pubmed: 26315529google scholar: lookup
  3. Kandahari AM, Yang X, Dighe AS, Pan D, Cui Q. Recognition of immune response for the early diagnosis and treatment of osteoarthritis.. J Immunol Res (2015) 2015:192415.
    doi: 10.1155/2015/192415pmc: PMC4433702pubmed: 26064995google scholar: lookup
  4. Orlowsky EW, Kraus VB. The role of innate immunity in osteoarthritis: when our first line of defense goes on the offensive.. J Rheumatol (2015) 42:363–71.
    doi: 10.3899/jrheum.140382pmc: PMC4465583pubmed: 25593231google scholar: lookup
  5. Bondeson J, Blom AB, Wainwright S, Hughes C, Caterson B, van den Berg WB. The role of synovial macrophages and macrophage-produced mediators in driving inflammatory and destructive responses in osteoarthritis.. Arthritis Rheum (2010) 62:647–57.
    doi: 10.1002/art.27290pubmed: 20187160google scholar: lookup
  6. Manferdini C, Paolella F, Gabusi E, Silvestri Y, Gambari L, Cattini L. From osteoarthritic synovium to synovial-derived cells characterization: synovial macrophages are key effector cells.. Arthritis Res Ther (2016) 18:83.
    doi: 10.1186/s13075-016-0983-4pmc: PMC4820904pubmed: 27044395google scholar: lookup
  7. Barrera P, Blom A, van Lent PL, van Bloois L, Beijnen JH, van Rooijen N. Synovial macrophage depletion with clodronate-containing liposomes in rheumatoid arthritis.. Arthritis Rheum (2000) 43:1951–9.
    doi: 10.1002/1529-0131(200009)43:9<1951::AID-ANR5>3.0.CO;2-Kpubmed: 11014344google scholar: lookup
  8. Van Lent PL, Van den Hoek AE, Van den Bersselaar LA, Spanjaards MF, Van Rooijen N, Dijkstra CD. In vivo role of phagocytic synovial lining cells in onset of experimental arthritis.. Am J Pathol (1993) 143:1226–37.
    pmc: PMC1887048pubmed: 8214013
  9. Wang Z, Zheng C, Zhong Y, He J, Cao X, Xia H. Interleukin-17 can induce osteoarthritis in rabbit knee joints similar to hulth's method.. Biomed Res Int (2017) 2017:11.
    doi: 10.1155/2017/2091325pmc: PMC5549504pubmed: 28815179google scholar: lookup
  10. Wu C-L, McNeill J, Goon K, Little D, Kimmerling K, Huebner J. Conditional macrophage depletion increases inflammation and does not inhibit the development of osteoarthritis in obese macrophage fas-induced apoptosis-transgenic mice.. Arthritis Rheumatol (2017) 69:1772–83.
    doi: 10.1002/art.40161pmc: PMC5611814pubmed: 28544542google scholar: lookup
  11. 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:R187.
    doi: 10.1186/ar2099pmc: PMC1794533pubmed: 17177994google scholar: lookup
  12. Iannone F, De Bari C, Dell'Accio F, Covelli M, Cantatore FP, Patella V. Interleukin-10 and interleukin-10 receptor in human osteoarthritic and healthy chondrocytes.. Clin Exp Rheumatol (2001) 19:139–45.
    pubmed: 11332442
  13. Mathiessen A, Conaghan PG. Synovitis in osteoarthritis: current understanding with therapeutic implications.. Arthritis Res Ther (2017) 19:18.
    doi: 10.1186/s13075-017-1229-9pmc: PMC5289060pubmed: 28148295google scholar: lookup
  14. Pessler F, Chen LX, Dai L, Gomez-Vaquero C, Diaz-Torne C, Paessler ME. A histomorphometric analysis of synovial biopsies from individuals with gulf war veterans' illness and joint pain compared to normal and osteoarthritis synovium.. Clin Rheumatol (2008) 27:1127–34.
    doi: 10.1007/s10067-008-0878-0pubmed: 18414968google scholar: lookup
  15. Kraus VB, McDaniel G, Huebner JL, Stabler TV, Pieper CF, Shipes SW. Direct in vivo evidence of activated macrophages in human osteoarthritis.. Osteoarthritis Cartilage (2016) 24:1613–21.
    doi: 10.1016/j.joca.2016.04.010pmc: PMC4992586pubmed: 27084348google scholar: lookup
  16. Wood MJ, Leckenby A, Reynolds G, Spiering R, Pratt AG, Rankin KS. Macrophage proliferation distinguishes 2 subgroups of knee osteoarthritis patients.. JCI insight (2019) 4:e125325.
    doi: 10.1172/jci.insight.125325pmc: PMC6413777pubmed: 30674730google scholar: lookup
  17. Fichadiya A, Bertram KL, Ren G, Yates RM, Krawetz RJ. Characterizing heterogeneity in the response of synovial mesenchymal progenitor cells to synovial macrophages in normal individuals and patients with osteoarthritis.. J Inflamm (2016) 13:12.
    doi: 10.1186/s12950-016-0120-9pmc: PMC4823907pubmed: 27057150google scholar: lookup
  18. Kennedy A, Fearon U, Veale DJ, Godson C. Macrophages in synovial inflammation.. Front Immunol (2011) 2:52.
    doi: 10.3389/fimmu.2011.00052pmc: PMC3342259pubmed: 22566842google scholar: lookup
  19. Bellac CL, Dufour A, Krisinger MJ, Loonchanta A, Starr AE, Auf dem Keller U. Macrophage matrix metalloproteinase-12 dampens inflammation and neutrophil influx in arthritis.. Cell Rep (2014) 9:618–32.
    doi: 10.1016/j.celrep.2014.09.006pubmed: 25310974google scholar: lookup
  20. Culemann S, Gruneboom A, Nicolas-Avila JA, Weidner D, Lammle KF, Rothe T. Locally renewing resident synovial macrophages provide a protective barrier for the joint.. Nature (2019) 572:670–5.
    doi: 10.1038/s41586-019-1471-1pmc: PMC6805223pubmed: 31391580google scholar: lookup
  21. Murray PJ, Allen JE, Biswas SK, Fisher EA, Gilroy DW, Goerdt S. Macrophage activation and polarization: nomenclature and experimental guidelines.. Immunity (2014) 41:14–20.
    doi: 10.1016/j.immuni.2014.06.008pmc: PMC4123412pubmed: 25035950google scholar: lookup
  22. Stables MJ, Shah S, Camon EB, Lovering RC, Newson J, Bystrom J. Transcriptomic analyses of murine resolution-phase macrophages.. Blood (2011) 118:e192–208.
    doi: 10.1182/blood-2011-04-345330pmc: PMC5362087pubmed: 22012065google scholar: lookup
  23. Buckley CD, Gilroy DW, Serhan CN. Proresolving lipid mediators and mechanisms in the resolution of acute inflammation.. Immunity (2014) 40:315–27.
    doi: 10.1016/j.immuni.2014.02.009pmc: PMC4004957pubmed: 24656045google scholar: lookup
  24. Godwin JW, Pinto AR, Rosenthal NA. Macrophages are required for adult salamander limb regeneration.. Proc Natl Acad Sci USA (2013) 110:9415–20.
    doi: 10.1073/pnas.1300290110pmc: PMC3677454pubmed: 23690624google scholar: lookup
  25. Feehan KT, Gilroy DW. Is resolution the end of inflammation?. Trends Mol Med (2019) 25:198–214.
    doi: 10.1016/j.molmed.2019.01.006pubmed: 30795972google scholar: lookup
  26. Fahy N, de Vries-van Melle ML, Lehmann J, Wei W, Grotenhuis N, Farrell E. Human osteoarthritic synovium impacts chondrogenic differentiation of mesenchymal stem cells via macrophage polarisation state.. Osteoarthritis Cartilage (2014) 22:1167–75.
    doi: 10.1016/j.joca.2014.05.021pubmed: 24911520google scholar: lookup
  27. Jain S, Tran TH, Amiji M. Macrophage repolarization with targeted alginate nanoparticles containing IL-10 plasmid DNA for the treatment of experimental arthritis.. Biomaterials (2015) 61:162–77.
    doi: 10.1016/j.biomaterials.2015.05.028pmc: PMC4464978pubmed: 26004232google scholar: lookup
  28. Menarim BG, Oliver KH, Mason A, Ngo C, Were Y, Barrett SR. LA Autologous bone marrow mononuclear cells modulate joint homeostasis in an equine in vivo model of synovitis.. FASEB J (2019) 33:14337–53.
    doi: 10.1096/fj.201901684RRpubmed: 31665925google scholar: lookup
  29. Gómez-Aristizábal A, Gandhi R, Mahomed NN, Marshall KW, Viswanathan S. Synovial fluid monocyte/macrophage subsets and their correlation to patient-reported outcomes in osteoarthritic patients: a cohort study.. Arthritis Res Ther (2019) 21:26.
    doi: 10.1186/s13075-018-1798-2pmc: PMC6339358pubmed: 30658702google scholar: lookup
  30. Liu B, Zhang M, Zhao J, Zheng M, Yang H. Imbalance of M1/M2 macrophages is linked to severity level of knee osteoarthritis.. Exp Ther Med (2018) 16:5009–14.
    doi: 10.3892/etm.2018.6852pmc: PMC6256852pubmed: 30546406google scholar: lookup
  31. Yarnall BW, Chamberlain CS, Hao Z, Muir P. Proinflammatory polarization of stifle synovial macrophages in dogs with cruciate ligament rupture.. Vet Surg (2019) 48:1005–12.
    doi: 10.1111/vsu.13261pubmed: 31190376google scholar: lookup
  32. Ross M. Diagnosis of lameness: movement.. In: Ross MW, Dyson S, editors. Diagnosis and Management of Lameness in the Horse. 2nd ed. St. Louis, MO: Elsevier Saunders; (2011). p. 72.
    doi: 10.1016/B978-1-4160-6069-7.00002-Xgoogle scholar: lookup
  33. McIlwraith CW, Frisbie DD, Kawcak CE, Fuller CJ, Hurtig M, Cruz A. The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the horse.. Osteoarthritis Cartilage (2010) 18(Suppl. 3):S93–105.
    doi: 10.1016/j.joca.2010.05.031pubmed: 20864027google scholar: lookup
  34. Sellam J, Berenbaum F. The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis.. Nature Rev Rheumatol (2010) 6:625.
    doi: 10.1038/nrrheum.2010.159pubmed: 20924410google scholar: lookup
  35. Krenn V, Morawietz L, Burmester G-R, Kinne RW, Mueller-Ladner U, Muller B. Synovitis score: discrimination between chronic low-grade and high-grade synovitis.. Histopathology (2006) 49:358–64.
    doi: 10.1111/j.1365-2559.2006.02508.xpubmed: 16978198google scholar: lookup
  36. Kamm JL, Nixon AJ, Witte TH. Cytokine and catabolic enzyme expression in synovium, synovial fluid and articular cartilage of naturally osteoarthritic equine carpi.. Equine Vet J (2010) 42:693–9.
    doi: 10.1111/j.2042-3306.2010.00140.xpmc: PMC4183755pubmed: 21039798google scholar: lookup
  37. Jayadev C, Rout R, Price A, Hulley P, Mahoney D. Hyaluronidase treatment of synovial fluid to improve assay precision for biomarker research using multiplex immunoassay platforms.. J Immunol Methods (2012) 386:22–30.
    doi: 10.1016/j.jim.2012.08.012pubmed: 22955210google scholar: lookup
  38. Benito MJ, Veale DJ, FitzGerald O, van den Berg WB, Bresnihan B. Synovial tissue inflammation in early and late osteoarthritis.. Ann Rheum Dis (2005) 64:1263–7.
    doi: 10.1136/ard.2004.025270pmc: PMC1755629pubmed: 15731292google scholar: lookup
  39. Zhang DE, Hetherington CJ, Gonzalez DA, Chen HM, Tenen DG. Regulation of CD14 expression during monocytic differentiation induced with 1 alpha,25-dihydroxyvitamin D3.. J Immunol (1994) 153:3276–84.
    pubmed: 7522257
  40. Fendl B, Weiss R, Eichhorn T, Spittler A, Fischer MB, Weber V. Storage of human whole blood, but not isolated monocytes, preserves the distribution of monocyte subsets.. Biophys Res Commun (2019) 517:709–14.
    doi: 10.1016/j.bbrc.2019.07.120pubmed: 31387744google scholar: lookup
  41. Lévêque M, Jeune KS-L, Jouneau S, Moulis S, Desrues B, Belleguic C. Soluble CD14 acts as a DAMP in human macrophages: origin and involvement in inflammatory cytokine/chemokine production.. FASEB J (2017) 31:1891–902.
    doi: 10.1096/fj.201600772Rpubmed: 28122919google scholar: lookup
  42. Safi W, Kuehnl A, Nüssler A, Eckstein H-H, Pelisek J. Differentiation of human CD14+ monocytes: an experimental investigation of the optimal culture medium and evidence of a lack of differentiation along the endothelial line.. Exp Mol Med (2016) 48:e227.
    doi: 10.1038/emm.2016.11pmc: PMC4855273pubmed: 27080367google scholar: lookup
  43. Zamani F, Zare Shahneh F, Aghebati-Maleki L, Baradaran B. Induction of CD14 expression and differentiation to monocytes or mature macrophages in promyelocytic cell lines: new approach.. Adv Pharm Bull (2013) 3:329–32.
    doi: 10.5681/apb.2013.053pmc: PMC3848216pubmed: 24312856google scholar: lookup
  44. Finnegan A, Ashaye S, Hamel KM. B effector cells in rheumatoid arthritis and experimental arthritis.. Autoimmunity (2012) 45:353–63.
    doi: 10.3109/08916934.2012.665526pmc: PMC3638788pubmed: 22432771google scholar: lookup
  45. Odobasic D, Leech MT, Xue JR, Holdsworth SR. Distinct in vivo roles of CD80 and CD86 in the effector T-cell responses inducing antigen-induced arthritis.. Immunology (2008) 124:503–13.
    doi: 10.1111/j.1365-2567.2007.02802.xpmc: PMC2492942pubmed: 18217945google scholar: lookup
  46. Zhou Y, Yoshida S, Kubo Y, Yoshimura T, Kobayashi Y, Nakama T. Different distributions of M1 and M2 macrophages in a mouse model of laser-induced choroidal neovascularization.. Mol Med Rep (2017) 15:3949–56.
    doi: 10.3892/mmr.2017.6491pmc: PMC5436148pubmed: 28440413google scholar: lookup
  47. Xue J, Schmidt SV, Sander J, Draffehn A, Krebs W, Quester I. Transcriptome-based network analysis reveals a spectrum model of human macrophage activation.. Immunity (2014) 40:274–88.
    doi: 10.1016/j.immuni.2014.01.006pmc: PMC3991396pubmed: 24530056google scholar: lookup
  48. Rivollier A, He J, Kole A, Valatas V, Kelsall BL. Inflammation switches the differentiation program of Ly6Chi monocytes from antiinflammatory macrophages to inflammatory dendritic cells in the colon.. J Exp Med (2012) 209:139–55.
    doi: 10.1084/jem.20101387pmc: PMC3260867pubmed: 22231304google scholar: lookup
  49. Nawaz A, Aminuddin A, Kado T, Takikawa A, Yamamoto S, Tsuneyama K. CD206+ M2-like macrophages regulate systemic glucose metabolism by inhibiting proliferation of adipocyte progenitors.. Nat Commun (2017) 8:286.
    doi: 10.1038/s41467-017-00231-1pmc: PMC5561263pubmed: 28819169google scholar: lookup
  50. Suzuki Y, Shirai M, Asada K, Yasui H, Karayama M, Hozumi H. Macrophage mannose receptor, CD206, predict prognosis in patients with pulmonary tuberculosis.. Sci Rep (2018) 8:13129.
    doi: 10.1038/s41598-018-31565-5pmc: PMC6120933pubmed: 30177769google scholar: lookup
  51. Jablonski KA, Amici SA, Webb LM, Ruiz-Rosado JdD, Popovich PG, Partida-Sanchez S. Novel markers to delineate murine M1 and M2 macrophages.. PLoS ONE (2015) 10:e0145342.
    doi: 10.1371/journal.pone.0145342pmc: PMC4689374pubmed: 26699615google scholar: lookup
  52. Martinez FO, Gordon S, Locati M, Mantovani A. Transcriptional profiling of the human monocyte-to-macrophage differentiation and polarization: new molecules and patterns of gene expression.. J Immunol (2006) 177:7303–11.
    doi: 10.4049/jimmunol.177.10.7303pubmed: 17082649google scholar: lookup
  53. Murray PJ. Macrophage polarization.. Ann Rev Physiol (2017) 79:541–66.
    doi: 10.1146/annurev-physiol-022516-034339pubmed: 27813830google scholar: lookup
  54. Behrendt P, Feldheim M, Preusse-Prange A, Weitkamp JT, Haake M, Eglin D. Chondrogenic potential of IL-10 in mechanically injured cartilage and cellularized collagen ACI grafts.. Osteoarthritis Cartilage (2018) 26:264–75.
    doi: 10.1016/j.joca.2017.11.007pubmed: 29169959google scholar: lookup
  55. King A, Balaji S, Le LD, Crombleholme TM, Keswani SG. Regenerative wound healing: the role of interleukin-10.. Adv Wound Care (2014) 3:315–23.
    doi: 10.1089/wound.2013.0461pmc: PMC3985521pubmed: 24757588google scholar: lookup
  56. Shapouri-Moghaddam A, Mohammadian S, Vazini H, Taghadosi M, Esmaeili SA, Mardani F. Macrophage plasticity, polarization, and function in health and disease.. J Cell Physiol (2018) 233:6425–40.
    doi: 10.1002/jcp.26429pubmed: 29319160google scholar: lookup
  57. Roszer T. Understanding the mysterious m2 macrophage through activation markers and effector mechanisms.. Mediators Inflamm (2015) 2015:16.
    doi: 10.1155/2015/816460pmc: PMC4452191pubmed: 26089604google scholar: lookup
  58. Ibrahim S, Steinbach F. Immunoprecipitation of equine CD molecules using anti-human MABs previously analyzed by flow cytometry and immunohistochemistry.. Vet Immunol Immunopathol (2012) 145:7–13.
    doi: 10.1016/j.vetimm.2011.07.021pubmed: 22070824google scholar: lookup
  59. Flaminio MJ, Borges AS, Nydam DV, Horohov DW, Hecker R, Matychak MB. The effect of CpG-ODN on antigen presenting cells of the foal.. J Immune Based Ther Vaccines (2007) 5:1.
    doi: 10.1186/1476-8518-5-1pmc: PMC1797044pubmed: 17254326google scholar: lookup
  60. Wagner B, Hillegas JM, Brinker DR, Horohov DW, Antczak DF. Characterization of monoclonal antibodies to equine interleukin-10 and detection of T regulatory 1 cells in horses.. Vet Immunol Immunopathol (2008) 122:57–64.
    doi: 10.1016/j.vetimm.2007.10.012pubmed: 18061278google scholar: lookup
  61. Kabithe E, Hillegas J, Stokol T, Moore J, Wagner B. Monoclonal antibodies to equine CD14.. Vet Immunol Immunopathol (2010) 138:149–53.
    doi: 10.1016/j.vetimm.2010.07.003pubmed: 20674042google scholar: lookup
  62. Prusov AN, Kolomijtseva G. Effect of UV-irradiation of rat liver nuclei on structural transitions and fractionation of the chromatin.. Biochemistry (1997) 62:667–75.
    pubmed: 9284549
  63. Tsuneyoshi Y, Tanaka M, Nagai T, Sunahara N, Matsuda T, Sonoda T. Functional folate receptor beta-expressing macrophages in osteoarthritis synovium and their M1/M2 expression profiles.. Scand J Rheumatol (2012) 41:132–40.
    doi: 10.3109/03009742.2011.605391pubmed: 22211358google scholar: lookup
  64. Menarim BC, Gillis KH, Oliver A, Mason C, Werre SR, Luo X. Inflamed synovial fluid induces a homeostatic response in bone marrow mononuclear cells in vitro: implications for joint therapy.. FASEB J (2020) 34:4430–44.
    doi: 10.1096/fj.201902698Rpubmed: 32030831google scholar: lookup
  65. Sergijenko A, Roelofs AJ, Riemen AHK, De Bari C. Bone marrow contribution to synovial hyperplasia following joint surface injury.. Arthritis Res Ther (2016) 18:166–66.
    doi: 10.1186/s13075-016-1060-8pmc: PMC4944318pubmed: 27412524google scholar: lookup
  66. Ryncarz RE, Anasetti C. Expression of CD86 on human marrow CD34(+) cells identifies immunocompetent committed precursors of macrophages and dendritic cells.. Blood (1998) 91:3892–900.
    doi: 10.1182/blood.V91.10.3892pubmed: 9573027google scholar: lookup
  67. St Clair EW. Interleukin 10 treatment for rheumatoid arthritis.. Ann Rheum Dis (1999) 58:I99–I102.
    doi: 10.1136/ard.58.2008.i99pmc: PMC1766579pubmed: 10577984google scholar: lookup
  68. Giraldi-Guimarães A, de Freitas HT, Coelho BdP, Macedo-Ramos H, Mendez-Otero R, Cavalcante LA. Bone marrow mononuclear cells and mannose receptor expression in focal cortical ischemia.. Brain Res (2012) 1452:173–84.
    doi: 10.1016/j.brainres.2012.03.002pubmed: 22459039google scholar: lookup
  69. Olingy CE, San Emeterio CL, Ogle ME, Krieger JR, Bruce AC, Pfau DD. Non-classical monocytes are biased progenitors of wound healing macrophages during soft tissue injury.. Sci Rep (2017) 7:447.
    doi: 10.1038/s41598-017-00477-1pmc: PMC5428475pubmed: 28348370google scholar: lookup
  70. Uderhardt S, Martins AJ, Tsang JS, Lammermann T, Germain RN. Resident macrophages cloak tissue microlesions to prevent neutrophil-driven inflammatory damage.. Cell (2019) 177:541–55.e17.
    doi: 10.1016/j.cell.2019.02.028pmc: PMC6474841pubmed: 30955887google scholar: lookup
  71. Zemans R, McClendon J, Jansing N, Ito Y, Redente E, Mason R. HIF1α dependent CXCR4/SDF1 signaling promotes alveolar type ii cell spreading and the restitution of epithelial barrier integrity after lung injury.. FASEB J (2015) 29:86314.
    doi: 10.1513/AnnalsATS.201411-545MGgoogle scholar: lookup
  72. Mills CD, Kincaid K, Alt JM, Heilman MJ, Hill AM. M-1/M-2 macrophages and the Th1/Th2 paradigm.. J Immunol (2000) 164:6166–73.
    doi: 10.4049/jimmunol.164.12.6166pubmed: 10843666google scholar: lookup
  73. Daghestani HN, Pieper CF, Kraus VB. Soluble macrophage biomarkers indicate inflammatory phenotypes in patients with knee osteoarthritis.. Arthritis Rheumatol (2015) 67:956–65.
    doi: 10.1002/art.39006pmc: PMC4441094pubmed: 25544994google scholar: lookup
  74. Vogel DY, Vereyken EJ, Glim JE, Heijnen PD, Moeton M, van der Valk P. Macrophages in inflammatory multiple sclerosis lesions have an intermediate activation status.. J Neuroinflamm (2013) 10:35.
    doi: 10.1186/1742-2094-10-35pmc: PMC3610294pubmed: 23452918google scholar: lookup
  75. de Waal Malefyt R, Abrams J, Bennett B, Figdor CG, de Vries JE. Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes.. J Exp Med (1991) 174:1209–20.
    doi: 10.1084/jem.174.5.1209pmc: PMC2119001pubmed: 1940799google scholar: lookup
  76. Lettesjo H, Nordstrom E, Strom H, Nilsson B, Glinghammar B, Dahlstedt L. Synovial fluid cytokines in patients with rheumatoid arthritis or other arthritic lesions.. Scand J Immunol (1998) 48:286–92.
    doi: 10.1046/j.1365-3083.1998.00399.xpubmed: 9743215google scholar: lookup
  77. Riyazi N, Slagboom E, de Craen AJ, Meulenbelt I, Houwing-Duistermaat JJ, Kroon HM. Association of the risk of osteoarthritis with high innate production of interleukin-1beta and low innate production of interleukin-10 ex vivo, upon lipopolysaccharide stimulation.. Arthritis Rheum (2005) 52:1443–50.
    doi: 10.1002/art.21014pubmed: 15880595google scholar: lookup
  78. Jansen NW, Roosendaal G, Hooiveld MJ, Bijlsma JW, van Roon JA, Theobald M. Interleukin-10 protects against blood-induced joint damage.. Br J Haematol (2008) 142:953–61.
    doi: 10.1111/j.1365-2141.2008.07278.xpubmed: 18637801google scholar: lookup
  79. Cush JJ, Splawski JB, Thomas R, McFarlin JE, Schulze-Koops H, Davis LS. Elevated interleukin-10 levels in patients with rheumatoid arthritis.. Arthritis Rheum (1995) 38:96–104.
    doi: 10.1002/art.1780380115pubmed: 7818579google scholar: lookup
  80. Goncars V, Kalnberzs K, Jakobsons E, Engele I, Briede I, Blums K. Treatment of knee osteoarthritis with bone marrow–derived mononuclear cell injection: 12-month follow-up.. Cartilage (2018) 10:26–35.
    doi: 10.1177/1947603517746721pmc: PMC6376566pubmed: 29373926google scholar: lookup
  81. Park M-J, Lee S-H, Kim E-K, Lee E-J, Baek J-A, Park S-H. Interleukin-10 produced by myeloid-derived suppressor cells is critical for the induction of Tregs and attenuation of rheumatoid inflammation in mice.. Sci Rep (2018) 8:3753.
    doi: 10.1038/s41598-018-21856-2pmc: PMC5830490pubmed: 29491381google scholar: lookup
  82. Stankovic A, Slavic V, Stamenkovic B, Kamenov B, Bojanovic M, Mitrovic DR. Serum and synovial fluid concentrations of CCL2 (MCP-1) chemokine in patients suffering rheumatoid arthritis and osteoarthritis reflect disease activity.. Bratisl Lek Listy (2009) 110:641–6.
    pubmed: 20017457
  83. Yuankun X, Yan K, Bin W, Jian-Hao L. Monocyte chemoattractant protein 1 induced chondrocytes degeneration and cartilage degradation in osteoarthritis.. Osteoarthritis Cartilage (2016) 24:S140–41.
    doi: 10.1016/j.joca.2016.01.275google scholar: lookup
  84. Haraden CA, Huebner JL, Hsueh MF, Li YJ, Kraus VB. Synovial fluid biomarkers associated with osteoarthritis severity reflect macrophage and neutrophil related inflammation.. Arthritis Res Ther (2019) 21:146.
    doi: 10.1186/s13075-019-1923-xpmc: PMC6567574pubmed: 31196179google scholar: lookup
  85. Akahoshi T, Wada C, Endo H, Hirota K, Hosaka S, Takagishi K. Expression of monocyte chemotactic and activating factor in rheumatoid arthritis. regulation of its production in synovial cells by interleukin-1 and tumor necrosis factor.. Arthritis Rheum (1993) 36:762–71.
    doi: 10.1002/art.1780360605pubmed: 8507217google scholar: lookup
  86. Yoshimura T. The chemokine MCP-1 (CCL2) in the host interaction with cancer: a foe or ally?. Cell Mol Immunol (2018) 15:335–45.
    doi: 10.1038/cmi.2017.135pmc: PMC6052833pubmed: 29375123google scholar: lookup
  87. Gu L, Tseng S, Horner RM, Tam C, Loda M, Rollins BJ. Control of TH2 polarization by the chemokine monocyte chemoattractant protein-1.. Nature (2000) 404:407–11.
    doi: 10.1038/35006097pubmed: 10746730google scholar: lookup
  88. Zhang J, Xiao Z, Qu C, Cui W, Wang X, Du J. CD8 T cells are involved in skeletal muscle regeneration through facilitating MCP-1 secretion and Gr1(high) macrophage infiltration.. J Immunol (2014) 193:5149.
    doi: 10.4049/jimmunol.1303486pubmed: 25339660google scholar: lookup
  89. Davies LC, Rosas M, Jenkins SJ, Liao C-T, Scurr MJ, Brombacher F. Distinct bone marrow-derived and tissue-resident macrophage lineages proliferate at key stages during inflammation.. Nat Commun (2013) 4:1886.
    doi: 10.1038/ncomms2877pmc: PMC3842019pubmed: 23695680google scholar: lookup
  90. Jenkins SJ, Ruckerl D, Thomas GD, Hewitson JP, Duncan S, Brombacher F. IL-4 directly signals tissue-resident macrophages to proliferate beyond homeostatic levels controlled by CSF-1.. J Exp Med (2013) 210:2477–91.
    doi: 10.1084/jem.20121999pmc: PMC3804948pubmed: 24101381google scholar: lookup
  91. Xu Q, Sun XC, Shang XP, Jiang HS. Association of CXCL12 levels in synovial fluid with the radiographic severity of knee osteoarthritis.. J Investig Med (2012) 60:898–901.
    doi: 10.2310/JIM.0b013e31825f9f69pubmed: 22751460google scholar: lookup
  92. Dymock DC, Brown MP, Merritt KA, Trumble TN. Concentrations of stromal cell-derived factor-1 in serum, plasma, and synovial fluid of horses with osteochondral injury.. Am J Vet Res (2014) 75:722–30.
    doi: 10.2460/ajvr.75.8.722pubmed: 25061703google scholar: lookup
  93. Wei L, Sun X, Kanbe K, Wang Z, Sun C, Terek R. Chondrocyte death induced by pathological concentration of chemokine stromal cell-derived factor-1.. J Rheumatol (2006) 33:1818–26.
    doi: 10.1016/j.humpath.2006.06.011pubmed: 16960943google scholar: lookup
  94. Lau TT, Wang DA. Stromal cell-derived factor-1 (SDF-1): homing factor for engineered regenerative medicine.. Expert Opin Biol Ther (2011) 11:189–97.
    doi: 10.1517/14712598.2011.546338pubmed: 21219236google scholar: lookup
  95. Morris EA, McDonald BS, Webb AC, Rosenwasser LJ. Identification of interleukin-1 in equine osteoarthritic joint effusions.. Am J Vet Res (1990) 51:59–64.
    pubmed: 2301820
  96. Morris EA, Treadwell BV. Effect of interleukin 1 on articular cartilage from young and aged horses and comparison with metabolism of osteoarthritic cartilage.. Am J Vet Res (1994) 55:138–46.
    pubmed: 8141486
  97. Caron JP, Fernandes JC, Martel-Pelletier J, Tardif G, Mineau F, Geng C. Chondroprotective effect of intraarticular injections of interleukin-1 receptor antagonist in experimental osteoarthritis. suppression of collagenase-1 expression.. Arthritis Rheum (1996) 39:1535–44.
    doi: 10.1002/art.1780390914pubmed: 8814066google scholar: lookup
  98. Goldring MB, Birkhead J, Sandell LJ, Krane SM. Synergistic regulation of collagen gene expression in human chondrocytes by tumor necrosis factor-α and interleukin-1β.. Ann N Y Acad Sci (1990) 580:536–9.
    doi: 10.1111/j.1749-6632.1990.tb17983.xgoogle scholar: lookup
  99. McNulty AL, Rothfusz NE, Leddy HA, Guilak F. Synovial fluid concentrations and relative potency of interleukin-1 alpha and beta in cartilage and meniscus degradation.. J Orthop Res (2013) 31:1039–45.
    doi: 10.1002/jor.22334pmc: PMC4037157pubmed: 23483596google scholar: lookup
  100. Ehrle A, Lischer CJ, Lasarzik J, Einspanier R, Bondzio A. Synovial fluid and serum concentrations of interleukin-1 receptor antagonist and interleukin-1ß in naturally occurring equine osteoarthritis and septic arthritis.. J Equine Vet Sci (2015) 35:815–22.
    doi: 10.1016/j.jevs.2015.07.023google scholar: lookup
  101. Theoret CL, Barber SM, Gordon JR. The expression of IL-1, IL-6, and TGF-β in the synovial fluid of horses with surgically-induced transient synovitis.. Vet Comp Orthop Traumatol (1998) 11:141–45.
    doi: 10.1055/s-0038-1632536google scholar: lookup
  102. Vendruscolo CdP, Moreira JJ, Seidel SRT, Fülber J, Neuenschwander HM, Bonagura G. Effects of medical ozone upon healthy equine joints: clinical and laboratorial aspects.. PLoS ONE (2018) 13:e0197736–e36.
    doi: 10.1371/journal.pone.0197736pmc: PMC5973567pubmed: 29813093google scholar: lookup
  103. Amin AR, Islam AB. Genomic analysis and differential expression of HMG and S100A family in human arthritis: upregulated expression of chemokines, IL-8 and nitric oxide by HMGB1.. DNA Cell Biol (2014) 33:550–65.
    doi: 10.1089/dna.2013.2198pmc: PMC4117271pubmed: 24905701google scholar: lookup
  104. Peffers MJ, McDermott B, Clegg PD, Riggs CM. Comprehensive protein profiling of synovial fluid in osteoarthritis following protein equalization.. Osteoarthritis Cartilage (2015) 23:1204–13.
    doi: 10.1016/j.joca.2015.03.019pmc: PMC4528073pubmed: 25819577google scholar: lookup
  105. Kirker-Head CA, Chandna VK, Agarwal RK, Morris EA, Tidwell A, O'Callaghan MW. Concentrations of substance P and prostaglandin E2 in synovial fluid of normal and abnormal joints of horses.. Am J Vet Res (2000) 61:714–8.
    doi: 10.2460/ajvr.2000.61.714pubmed: 10850851google scholar: lookup
  106. van de Water E, Oosterlinck M, Dumoulin M, Korthagen NM, van Weeren PR, van den Broek J. The preventive effects of two nutraceuticals on experimentally induced acute synovitis.. Equine Vet J (2017) 49:532–38.
    doi: 10.1111/evj.12629pmc: PMC5484312pubmed: 27554764google scholar: lookup
  107. Manferdini C, Maumus M, Gabusi E, Piacentini A, Filardo G, Peyrafitte J-A. Adipose-derived mesenchymal stem cells exert antiinflammatory effects on chondrocytes and synoviocytes from osteoarthritis patients through prostaglandin E2.. Arthritis Rheum (2013) 65:1271–81.
    doi: 10.1002/art.37908pubmed: 23613363google scholar: lookup
  108. Levy BD, Clish CB, Schmidt B, Gronert K, Serhan CN. Lipid mediator class switching during acute inflammation: signals in resolution.. Nat Immunol (2001) 2:612–9.
    doi: 10.1038/89759pubmed: 11429545google scholar: lookup
  109. Menarim BC, Vasconcelos Machado VM, Cisneros Alvarez LE, Carneiro R, Busch L, Vulcano LC. Radiographic abnormalities in barrel racing horses with lameness referable to the metacarpophalangeal joint.. J Equine Vet Sci (2012) 32:216–21.
    doi: 10.1016/j.jevs.2011.09.064google scholar: lookup
  110. Mora-Carreño M, Briones R, Galecio J, Parra D, Rosenfeld C, Schmeisser A. Main musculoskeletal injuries associated with lameness in chilean rodeo horses.. Arch Med Vet (2014) 46:419–24.
    doi: 10.4067/S0301-732X2014000300011google scholar: lookup
  111. Hill WT. On-the-track catastrophe in the thoroughbred racehorse.. In: Ross MW, Dyson S, editors. Diagnosis and Management of Lameness in the Horse. 2nd ed St. Louis, MO: Elsevier; (2011). p. 960–68.
    doi: 10.1016/B978-1-4160-6069-7.00103-6google scholar: lookup
  112. Garcia J, Hulme C, Mennan C, Roberts S, Bastiaansen-Jenniskens YM, van Osch GJVM. The synovial fluid from patients with focal cartilage defects contains mesenchymal stem/stromal cells and macrophages with pro- and anti-inflammatory phenotypes.. Osteoarthr Cartil Open (2020) 2:100039.
    doi: 10.1016/j.ocarto.2020.100039pmc: PMC9718259pubmed: 36474589google scholar: lookup
  113. Davies CL, Patir A, McColl BW. Myeloid cell and transcriptome signatures associated with inflammation resolution in a model of self-limiting acute brain inflammation.. Front Immunol (2019) 10:1048.
    doi: 10.3389/fimmu.2019.01048pmc: PMC6533855pubmed: 31156629google scholar: lookup

Citations

This article has been cited 24 times.
  1. Chaimbeul SF, Rodrigues NNP, Thurston DD, Scoggin KE, Janes J, Jacobs CA, MacLeod JN, Stone AV, Menarim BC. PPARγ Agonism Modulates Synovial Macrophage and Cartilage Responses in an Equine Model of Synovial Inflammation-Implications for Joint Therapy. Biomolecules 2025 Sep 1;15(9).
    doi: 10.3390/biom15091267pubmed: 41008574google scholar: lookup
  2. Blanco AF, Lou G, Pensado-López A, Ummarino A, Andón FT, Crecente-Campo J, Alonso MJ. Controlled co-delivery of anti-inflammatory drugs from bilayer polymer films coating a meniscus implant. Drug Deliv Transl Res 2025 Aug 25;.
    doi: 10.1007/s13346-025-01942-5pubmed: 40853537google scholar: lookup
  3. Bertone AL, Reinemeyer C, Tsaprailis G, Ragland D, Leise B. Cryopreserved equine umbilical cord tissue allograft characterization and biocompatibility in vivo in musculoskeletal tissues: a controlled study. BMC Med 2025 Jul 23;23(1):439.
    doi: 10.1186/s12916-025-04231-7pubmed: 40702469google scholar: lookup
  4. Deng W, Wang T, Li L, Xiao X, Xu Y, Li Q, Zhou Q, Yin Y, Yang H, Gong K, Zhou Y, Wang Y. A review of nanomaterials in osteoarthritis treatment and immune modulation. Regen Biomater 2025;12:rbaf048.
    doi: 10.1093/rb/rbaf048pubmed: 40556785google scholar: lookup
  5. Moore GE, Leatherwood JL, Glass KG, Arnold CE, Paris BL, Carter MM, George JM, Fontenot AB, Martinez RE, Franklin MA, Norton SA, Bradbery AN, Wickersham TA. Influence of dietary Saccharomyces cerevisiae fermentation product on markers of inflammation and cartilage metabolism in young exercising horses challenged with intra-articular lipopolysaccharide. Transl Anim Sci 2025;9:txaf042.
    doi: 10.1093/tas/txaf042pubmed: 40336821google scholar: lookup
  6. Guerra-Gomes M, Ferreira-Baptista C, Barros J, Alves-Pimenta S, Gomes P, Colaço B. Exploring the Potential of Non-Cellular Orthobiologic Products in Regenerative Therapies for Stifle Joint Diseases in Companion Animals. Animals (Basel) 2025 Feb 18;15(4).
    doi: 10.3390/ani15040589pubmed: 40003071google scholar: lookup
  7. Gao Q, Zhang X, Makarcyzk MJ, Wong LE, Quig MSV, Shinohara I, Murayama M, Chow SK, Bunnell BA, Lin H, Goodman SB. Macrophage phenotypes modulate neoangiogenesis and fibroblast profiles in synovial-like organoid cultures. Osteoarthritis Cartilage 2025 May;33(5):590-600.
    doi: 10.1016/j.joca.2025.02.777pubmed: 39978574google scholar: lookup
  8. Lu P, Li Y, Yang S, Yao H, Tu B, Ning R. B Cell Activation, Differentiation, and Their Potential Molecular Mechanisms in Osteoarthritic Synovial Tissue. J Inflamm Res 2025;18:2137-2151.
    doi: 10.2147/JIR.S503597pubmed: 39959649google scholar: lookup
  9. Cardeti G, Manna G, Cersini A, Nardini R, Rosati S, Reina R, Cittadini M, Sittinieri S, Altigeri A, Marcario GA, Scicluna MT. Horse Innate Immunity in the Control of Equine Infectious Anemia Virus Infection: A Preliminary Study. Viruses 2024 Nov 21;16(12).
    doi: 10.3390/v16121804pubmed: 39772115google scholar: lookup
  10. Gagliardi R, Koch DW, Loeser R, Schnabel LV. Matrikine stimulation of equine synovial fibroblasts and chondrocytes results in an in vitro osteoarthritis phenotype. J Orthop Res 2025 Feb;43(2):292-303.
    doi: 10.1002/jor.26004pubmed: 39486895google scholar: lookup
  11. Huang L, Yao Y, Ruan Z, Zhang S, Feng X, Lu C, Zhao J, Yin F, Cao C, Zheng L. Baicalin nanodelivery system based on functionalized metal-organic framework for targeted therapy of osteoarthritis by modulating macrophage polarization. J Nanobiotechnology 2024 May 9;22(1):221.
    doi: 10.1186/s12951-024-02494-5pubmed: 38724958google scholar: lookup
  12. Everett JB, Menarim BC, Barrett SH, Bogers SH, Byron CR, Pleasant RS, Werre SR, Dahlgren LA. Intra-articular bone marrow mononuclear cell therapy improves lameness from naturally occurring equine osteoarthritis. Front Vet Sci 2023;10:1256284.
    doi: 10.3389/fvets.2023.1256284pubmed: 37876630google scholar: lookup
  13. Laus F, Gialletti R, Bazzano M, Laghi L, Dini F, Marchegiani A. Synovial Fluid Metabolome Can Differentiate between Healthy Joints and Joints Affected by Osteoarthritis in Horses. Metabolites 2023 Aug 4;13(8).
    doi: 10.3390/metabo13080913pubmed: 37623857google scholar: lookup
  14. Keller LE, Tait Wojno ED, Begum L, Fortier LA. T Helper 17-Like Regulatory T Cells in Equine Synovial Fluid Are Associated With Disease Severity of Naturally Occurring Posttraumatic Osteoarthritis. Am J Sports Med 2023 Mar;51(4):1047-1058.
    doi: 10.1177/03635465231153588pubmed: 36794851google scholar: lookup
  15. Xu M, Ji Y. Immunoregulation of synovial macrophages for the treatment of osteoarthritis. Open Life Sci 2023;18(1):20220567.
    doi: 10.1515/biol-2022-0567pubmed: 36789002google scholar: lookup
  16. Liu Y, Lu T, Liu Z, Ning W, Li S, Chen Y, Ge X, Guo C, Zheng Y, Wei X, Wang H. Six macrophage-associated genes in synovium constitute a novel diagnostic signature for osteoarthritis. Front Immunol 2022;13:936606.
    doi: 10.3389/fimmu.2022.936606pubmed: 35967352google scholar: lookup
  17. Mushenkova NV, Nikiforov NG, Shakhpazyan NK, Orekhova VA, Sadykhov NK, Orekhov AN. Phenotype Diversity of Macrophages in Osteoarthritis: Implications for Development of Macrophage Modulating Therapies. Int J Mol Sci 2022 Jul 29;23(15).
    doi: 10.3390/ijms23158381pubmed: 35955514google scholar: lookup
  18. Baccarin RYA, Seidel SRT, Michelacci YM, Tokawa PKA, Oliveira TM. Osteoarthritis: a common disease that should be avoided in the athletic horse's life. Anim Front 2022 Jun;12(3):25-36.
    doi: 10.1093/af/vfac026pubmed: 35711506google scholar: lookup
  19. Pang QM, Yang R, Zhang M, Zou WH, Qian NN, Xu QJ, Chen H, Peng JC, Luo XP, Zhang Q, Zhang T. Peripheral Blood-Derived Mesenchymal Stem Cells Modulate Macrophage Plasticity through the IL-10/STAT3 Pathway. Stem Cells Int 2022;2022:5181241.
    doi: 10.1155/2022/5181241pubmed: 35450344google scholar: lookup
  20. Vincent TL, Alliston T, Kapoor M, Loeser RF, Troeberg L, Little CB. Osteoarthritis Pathophysiology: Therapeutic Target Discovery may Require a Multifaceted Approach. Clin Geriatr Med 2022 May;38(2):193-219.
    doi: 10.1016/j.cger.2021.11.015pubmed: 35410676google scholar: lookup
  21. Menarim BC, El-Sheikh Ali H, Loux SC, Scoggin KE, Kalbfleisch TS, MacLeod JN, Dahlgren LA. Transcriptional and Histochemical Signatures of Bone Marrow Mononuclear Cell-Mediated Resolution of Synovitis. Front Immunol 2021;12:734322.
    doi: 10.3389/fimmu.2021.734322pubmed: 34956173google scholar: lookup
  22. Gao Q, Li Z, Rhee C, Xiang S, Maruyama M, Huang EE, Yao Z, Bunnell BA, Tuan RS, Lin H, Gold MS, Goodman SB. Macrophages Modulate the Function of MSC- and iPSC-Derived Fibroblasts in the Presence of Polyethylene Particles. Int J Mol Sci 2021 Nov 27;22(23).
    doi: 10.3390/ijms222312837pubmed: 34884641google scholar: lookup
  23. Estrada McDermott J, Pezzanite L, Goodrich L, Santangelo K, Chow L, Dow S, Wheat W. Role of Innate Immunity in Initiation and Progression of Osteoarthritis, with Emphasis on Horses. Animals (Basel) 2021 Nov 13;11(11).
    doi: 10.3390/ani11113247pubmed: 34827979google scholar: lookup
  24. Menarim BC, MacLeod JN, Dahlgren LA. Bone marrow mononuclear cells for joint therapy: The role of macrophages in inflammation resolution and tissue repair. World J Stem Cells 2021 Jul 26;13(7):825-840.
    doi: 10.4252/wjsc.v13.i7.825pubmed: 34367479google scholar: lookup
Subscribe to our newsletter
Join 99,344 horse owners like you who receive our email updates on horse health and nutrition.