FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / Vet Immunol Immunopathol / Cloning and expression of ADAM-related metalloproteases in e...
Veterinary immunology and immunopathology2008; 129(3-4); 231-241; doi: 10.1016/j.vetimm.2008.11.022

Cloning and expression of ADAM-related metalloproteases in equine laminitis.

Abstract: Equine laminitis is a debilitating disease affecting the digital laminae that suspend the distal phalanx within the hoof. While the clinical progression of the disease has been well documented, the molecular events associated with its pathogenesis remain largely unknown. Using real time quantitative PCR (RT-qPCR), we have investigated the expression of genes coding for proteins containing a Disintegrin and Metalloprotease domain (ADAM), as well as genes encoding the natural inhibitors of these enzymes (tissue inhibitor of metalloprotease; TIMP) in horses with naturally-acquired (acute, chronic and aggravated chronic clinical cases) or experimentally-induced (black walnut extract (BWE) and starch gruel models) laminitis. Changes in expression of these enzymes and regulators may underlie the pathologic remodeling of lamellar tissue in laminitis. Genes encoding ADAMs involved in inflammation (ADAM-10 and ADAM-17), as well as those implicated in arthritis (ADAMTS-1, ADAMTS-4 and ADAMTS-5) were cloned, and the sequences used to generate specific oligonucleotide primers for the RT-qPCR experiments. Our results show that genes encoding ADAM-10 and ADAM-17 were not induced in most laminitic animals, whereas ADAMTS-4 gene expression was strongly upregulated in nearly all horses with experimentally-induced and naturally-acquired laminitis. The expression of matrix metalloproteases (MMP)-9 and ADAMTS-5 was also increased in many of the laminitic horses. In addition, TIMP-2 gene expression was decreased in most laminitic horses, whereas expression of genes encoding other TIMPs, namely TIMP-1 and TIMP-3, was randomly increased or decreased in the various models. We conclude that increased expression of lamellar ADAMTS-4 is a common feature of laminitis consistent with a central role of the gene product in the pathophysiology of the disease.
Get Full Text
Publication Date: 2008-11-25 PubMed ID: 19131116PubMed Central: PMC2907504DOI: 10.1016/j.vetimm.2008.11.022Google 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
  • Research Support
  • N.I.H.
  • Extramural
  • Research Support
  • Non-U.S. Gov't
  • Research Support
  • U.S. Gov't
  • Non-P.H.S.

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 describes an investigation into the role of enzymes and their natural inhibitors in equine laminitis, a debilitating disease in horses. Findings suggest that an increased expression of a particular enzyme, ADAMTS-4, may be a key factor in the disease’s pathophysiology.

Introduction

  • Equine laminitis is a severe illness that impacts the digital laminae in horses, suspending the distal phalanx inside the hoof. While the clinical advancement of the disease is understood, the study focuses on revealing the lesser-known molecular aspects associated with its cause.

Methodology and Research Objective

  • Researchers utilise Real Time Quantitative PCR (RT-qPCR) to explore the expression of genes involved in proteins that contain a Disintegrin and Metalloprotease domain (ADAMs). They also study genes encoding tissue inhibitor of metalloprotease (TIMP), an enzyme regulator.
  • The study focuses on horses with naturally-acquired (acute, chronic and aggravated chronic clinical cases) or experimentally-induced laminitis (using black walnut extract and starch gruel models).
  • The primary objective is to uncover if changes in the expression of these enzymes and regulators may underlie the pathologic remodelling of lamellar tissue in laminitis.

Results

  • ADAMs associated with inflammation (ADAM-10 and ADAM-17) and those linked to arthritis (ADAMTS-1, ADAMTS-4, and ADAMTS-5) were cloned for further research.
  • The expression of ADAM-10 and ADAM-17 was not induced in the majority of laminitic horses. However, the ADAMTS-4 gene expression was strongly upregulated (increased) in nearly all horses with experimentally and naturally acquired laminitis.
  • Increased expression of matrix metalloproteases (MMP)-9 and ADAMTS-5 was also noted in many laminitic horses.
  • On the contrary, TIMP-2 gene expression was decreased in the majority of laminitic horses. The expression of genes encoding other TIMPs (TIMP-1 and TIMP-3) displayed mixed results, with randomly increased or decreased expression in various samples.

Conclusion

  • The research concludes that an increased expression of the ADAMTS-4 enzyme is critically associated with laminitis, indicating its potential role in the disease’s pathophysiology. This finding provides a new perspective to understand and address equine laminitis from a molecular standpoint.

Cite This Article

APA
Coyne MJ, Cousin H, Loftus JP, Johnson PJ, Belknap JK, Gradil CM, Black SJ, Alfandari D. (2008). Cloning and expression of ADAM-related metalloproteases in equine laminitis. Vet Immunol Immunopathol, 129(3-4), 231-241. https://doi.org/10.1016/j.vetimm.2008.11.022

Publication

Veterinary immunology and immunopathology
ISSN: 0165-2427
NlmUniqueID: 8002006
Country: Netherlands
Language: English
Volume: 129
Issue: 3-4
Pages: 231-241

Researcher Affiliations

Coyne, Michael J
  • Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003, United States.
Cousin, Hélène
    Loftus, John P
      Johnson, Philip J
        Belknap, James K
          Gradil, Carlos M
            Black, Samuel J
              Alfandari, Dominique

                MeSH Terms

                • ADAM Proteins / genetics
                • ADAM Proteins / metabolism
                • Animals
                • Base Sequence
                • Cloning, Molecular
                • Foot Diseases / chemically induced
                • Foot Diseases / enzymology
                • Foot Diseases / genetics
                • Foot Diseases / veterinary
                • Gene Expression Profiling
                • Gene Expression Regulation, Enzymologic / physiology
                • Hoof and Claw
                • Horse Diseases / chemically induced
                • Horse Diseases / enzymology
                • Horse Diseases / genetics
                • Horses
                • Inflammation / chemically induced
                • Inflammation / enzymology
                • Inflammation / veterinary
                • Molecular Sequence Data

                Grant Funding

                • R01 DE016289-03 / NIDCR NIH HHS
                • R01 DE016289-01A2 / NIDCR NIH HHS
                • R01 DE016289-02 / NIDCR NIH HHS
                • R01 DE016289 / NIDCR NIH HHS
                • DE016289 / NIDCR NIH HHS
                • R01 DE016289-04 / NIDCR NIH HHS

                References

                This article includes 74 references
                1. Alfandari D, Cousin H, Gaultier A, Smith K, White JM, Darribère T, DeSimone DW. Xenopus ADAM 13 is a metalloprotease required for cranial neural crest-cell migration.. Curr Biol 2001 Jun 26;11(12):918-30.
                  pubmed: 11448768doi: 10.1016/s0960-9822(01)00263-9google scholar: lookup
                2. Alfandari D, Whittaker CA, DeSimone DW, Darribère T. Integrin alpha v subunit is expressed on mesodermal cell surfaces during amphibian gastrulation.. Dev Biol 1995 Aug;170(2):249-61.
                  pubmed: 7649360doi: 10.1006/dbio.1995.1212google scholar: lookup
                3. Amour A, Knight CG, Webster A, Slocombe PM, Stephens PE, Knäuper V, Docherty AJ, Murphy G. The in vitro activity of ADAM-10 is inhibited by TIMP-1 and TIMP-3.. FEBS Lett 2000 May 19;473(3):275-9.
                  pubmed: 10818225doi: 10.1016/s0014-5793(00)01528-3google scholar: lookup
                4. Amour A, Slocombe PM, Webster A, Butler M, Knight CG, Smith BJ, Stephens PE, Shelley C, Hutton M, Knäuper V, Docherty AJ, Murphy G. TNF-alpha converting enzyme (TACE) is inhibited by TIMP-3.. FEBS Lett 1998 Sep 11;435(1):39-44.
                  pubmed: 9755855doi: 10.1016/s0014-5793(98)01031-xgoogle scholar: lookup
                5. Belknap JK, Giguère S, Pettigrew A, Cochran AM, Van Eps AW, Pollitt CC. Lamellar pro-inflammatory cytokine expression patterns in laminitis at the developmental stage and at the onset of lameness: innate vs. adaptive immune response.. Equine Vet J 2007 Jan;39(1):42-7.
                  pubmed: 17228594doi: 10.2746/042516407x155406google scholar: lookup
                6. Black RA, Rauch CT, Kozlosky CJ, Peschon JJ, Slack JL, Wolfson MF, Castner BJ, Stocking KL, Reddy P, Srinivasan S, Nelson N, Boiani N, Schooley KA, Gerhart M, Davis R, Fitzner JN, Johnson RS, Paxton RJ, March CJ, Cerretti DP. A metalloproteinase disintegrin that releases tumour-necrosis factor-alpha from cells.. Nature 1997 Feb 20;385(6618):729-33.
                  pubmed: 9034190doi: 10.1038/385729a0google scholar: lookup
                7. Black SJ, Lunn DP, Yin C, Hwang M, Lenz SD, Belknap JK. Leukocyte emigration in the early stages of laminitis.. Vet Immunol Immunopathol 2006 Jan 15;109(1-2):161-6.
                  pubmed: 16169600doi: 10.1016/j.vetimm.2005.08.017google scholar: lookup
                8. Blikslager AT, Yin C, Cochran AM, Wooten JG, Pettigrew A, Belknap JK. Cyclooxygenase expression in the early stages of equine laminitis: a cytologic study.. J Vet Intern Med 2006 Sep-Oct;20(5):1191-6.
                  pubmed: 17063715doi: 10.1892/0891-6640(2006)20[1191:ceites]2.0.co;2google scholar: lookup
                9. Blobel CP. ADAMs: key components in EGFR signalling and development.. Nat Rev Mol Cell Biol 2005 Jan;6(1):32-43.
                  pubmed: 15688065doi: 10.1038/nrm1548google scholar: lookup
                10. Chakrabarti S, Patel KD. Regulation of matrix metalloproteinase-9 release from IL-8-stimulated human neutrophils.. J Leukoc Biol 2005 Jul;78(1):279-88.
                  pubmed: 15831558doi: 10.1189/jlb.1004612google scholar: lookup
                11. Clegg PD, Jones MD, Carter SD. The effect of drugs commonly used in the treatment of equine articular disorders on the activity of equine matrix metalloproteinase-2 and 9.. J Vet Pharmacol Ther 1998 Oct;21(5):406-13.
                  pubmed: 9811443doi: 10.1046/j.1365-2885.1998.00157.xgoogle scholar: lookup
                12. Cousin H, Gaultier A, Bleux C, Darribère T, Alfandari D. PACSIN2 is a regulator of the metalloprotease/disintegrin ADAM13.. Dev Biol 2000 Nov 1;227(1):197-210.
                  pubmed: 11076687doi: 10.1006/dbio.2000.9871google scholar: lookup
                13. Cross NA, Chandrasekharan S, Jokonya N, Fowles A, Hamdy FC, Buttle DJ, Eaton CL. The expression and regulation of ADAMTS-1, -4, -5, -9, and -15, and TIMP-3 by TGFbeta1 in prostate cells: relevance to the accumulation of versican.. Prostate 2005 May 15;63(3):269-75.
                  pubmed: 15599946doi: 10.1002/pros.20182google scholar: lookup
                14. Fontaine GL, Belknap JK, Allen D, Moore JN, Kroll DL. Expression of interleukin-1beta in the digital laminae of horses in the prodromal stage of experimentally induced laminitis.. Am J Vet Res 2001 May;62(5):714-20.
                  pubmed: 11341391doi: 10.2460/ajvr.2001.62.714google scholar: lookup
                15. French KR, Pollitt CC. Equine laminitis: loss of hemidesmosomes in hoof secondary epidermal lamellae correlates to dose in an oligofructose induction model: an ultrastructural study.. Equine Vet J 2004 Apr;36(3):230-5.
                  pubmed: 15147130doi: 10.2746/0425164044877125google scholar: lookup
                16. Galey FD, Beasley VR, Schaeffer D, Davis LE. Effect of an aqueous extract of black walnut (Juglans nigra) on isolated equine digital vessels.. Am J Vet Res 1990 Jan;51(1):83-8.
                  pubmed: 2301825
                17. Galey FD, Whiteley HE, Goetz TE, Kuenstler AR, Davis CA, Beasley VR. Black walnut (Juglans nigra) toxicosis: a model for equine laminitis.. J Comp Pathol 1991 Apr;104(3):313-26.
                  pubmed: 2061431doi: 10.1016/s0021-9975(08)80043-6google scholar: lookup
                18. Garner HE, Coffman JR, Hahn AW, Hutcheson DP, Tumbleson ME. Equine laminitis of alimentary origin: an experimental model.. Am J Vet Res 1975 Apr;36(4 Pt.1):441-4.
                  pubmed: 1124880
                19. Garton KJ, Gough PJ, Blobel CP, Murphy G, Greaves DR, Dempsey PJ, Raines EW. Tumor necrosis factor-alpha-converting enzyme (ADAM17) mediates the cleavage and shedding of fractalkine (CX3CL1).. J Biol Chem 2001 Oct 12;276(41):37993-8001.
                  pubmed: 11495925doi: 10.1074/jbc.M106434200google scholar: lookup
                20. Gomez DE, De Lorenzo MS, Alonso DF, Andrade ZA. Expression of metalloproteinases (MMP-1, MMP-2, and MMP-9) and their inhibitors (TIMP-1 and TIMP-2) in schistosomal portal fibrosis.. Am J Trop Med Hyg 1999 Jul;61(1):9-13.
                  pubmed: 10432047doi: 10.4269/ajtmh.1999.61.9google scholar: lookup
                21. Grosenbaugh DA, Morgan SJ, Hood DM. The digital pathologies of chronic laminitis.. Vet Clin North Am Equine Pract 1999 Aug;15(2):419-36.
                  pubmed: 10472120doi: 10.1016/s0749-0739(17)30153-0google scholar: lookup
                22. Han YP. Matrix metalloproteinases, the pros and cons, in liver fibrosis.. J Gastroenterol Hepatol 2006 Oct;21 Suppl 3(Suppl 3):S88-91.
                  pmc: PMC2646497pubmed: 16958682doi: 10.1111/j.1440-1746.2006.04586.xgoogle scholar: lookup
                23. Hashimoto G, Aoki T, Nakamura H, Tanzawa K, Okada Y. Inhibition of ADAMTS4 (aggrecanase-1) by tissue inhibitors of metalloproteinases (TIMP-1, 2, 3 and 4).. FEBS Lett 2001 Apr 13;494(3):192-5.
                  pubmed: 11311239doi: 10.1016/s0014-5793(01)02323-7google scholar: lookup
                24. Hashimoto G, Shimoda M, Okada Y. ADAMTS4 (aggrecanase-1) interaction with the C-terminal domain of fibronectin inhibits proteolysis of aggrecan.. J Biol Chem 2004 Jul 30;279(31):32483-91.
                  pubmed: 15161923doi: 10.1074/jbc.M314216200google scholar: lookup
                25. Homandberg GA, Meyers R, Xie DL. Fibronectin fragments cause chondrolysis of bovine articular cartilage slices in culture.. J Biol Chem 1992 Feb 25;267(6):3597-604.
                  pubmed: 1740411
                26. Hu J, Van den Steen PE, Sang QX, Opdenakker G. Matrix metalloproteinase inhibitors as therapy for inflammatory and vascular diseases.. Nat Rev Drug Discov 2007 Jun;6(6):480-98.
                  pubmed: 17541420doi: 10.1038/nrd2308google scholar: lookup
                27. Hudson MP, Armstrong PW, Ruzyllo W, Brum J, Cusmano L, Krzeski P, Lyon R, Quinones M, Theroux P, Sydlowski D, Kim HE, Garcia MJ, Jaber WA, Weaver WD. Effects of selective matrix metalloproteinase inhibitor (PG-116800) to prevent ventricular remodeling after myocardial infarction: results of the PREMIER (Prevention of Myocardial Infarction Early Remodeling) trial.. J Am Coll Cardiol 2006 Jul 4;48(1):15-20.
                  pubmed: 16814643doi: 10.1016/j.jacc.2006.02.055google scholar: lookup
                28. Hurley DJ, Parks RJ, Reber AJ, Donovan DC, Okinaga T, Vandenplas ML, Peroni JF, Moore JN. Dynamic changes in circulating leukocytes during the induction of equine laminitis with black walnut extract.. Vet Immunol Immunopathol 2006 Apr 15;110(3-4):195-206.
                  pubmed: 16290066doi: 10.1016/j.vetimm.2005.09.015google scholar: lookup
                29. Johnson PJ, Kreeger JM, Keeler M, Ganjam VK, Messer NT. Serum markers of lamellar basement membrane degradation and lamellar histopathological changes in horses affected with laminitis.. Equine Vet J 2000 Nov;32(6):462-8.
                  pubmed: 11093618doi: 10.2746/042516400777584695google scholar: lookup
                30. Johnson PJ, Tyagi SC, Katwa LC, Ganjam VK, Moore LA, Kreeger JM, Messer NT. Activation of extracellular matrix metalloproteinases in equine laminitis.. Vet Rec 1998 Apr 11;142(15):392-6.
                  pubmed: 9586131doi: 10.1136/vr.142.15.392google scholar: lookup
                31. Kähäri VM, Saarialho-Kere U. Matrix metalloproteinases and their inhibitors in tumour growth and invasion.. Ann Med 1999 Feb;31(1):34-45.
                  pubmed: 10219712doi: 10.3109/07853899909019260google scholar: lookup
                32. Kashiwagi M, Tortorella M, Nagase H, Brew K. TIMP-3 is a potent inhibitor of aggrecanase 1 (ADAM-TS4) and aggrecanase 2 (ADAM-TS5).. J Biol Chem 2001 Apr 20;276(16):12501-4.
                  pubmed: 11278243doi: 10.1074/jbc.C000848200google scholar: lookup
                33. Kim T, Oh J, Woo JM, Choi E, Im SH, Yoo YJ, Kim DH, Nishimura H, Cho C. Expression and relationship of male reproductive ADAMs in mouse.. Biol Reprod 2006 Apr;74(4):744-50.
                  pubmed: 16407499doi: 10.1095/biolreprod.105.048892google scholar: lookup
                34. Kyaw-Tanner M, Pollitt CC. Equine laminitis: increased transcription of matrix metalloproteinase-2 (MMP-2) occurs during the developmental phase.. Equine Vet J 2004 Apr;36(3):221-5.
                  pubmed: 15147128doi: 10.2746/0425164044877242google scholar: lookup
                35. Little CB, Hughes CE, Curtis CL, Janusz MJ, Bohne R, Wang-Weigand S, Taiwo YO, Mitchell PG, Otterness IG, Flannery CR, Caterson B. Matrix metalloproteinases are involved in C-terminal and interglobular domain processing of cartilage aggrecan in late stage cartilage degradation.. Matrix Biol 2002 Apr;21(3):271-88.
                  pubmed: 12009333doi: 10.1016/s0945-053x(02)00004-5google scholar: lookup
                36. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.. Methods 2001 Dec;25(4):402-8.
                  pubmed: 11846609doi: 10.1006/meth.2001.1262google scholar: lookup
                37. Loftus JP, Belknap JK, Black SJ. Matrix metalloproteinase-9 in laminae of black walnut extract treated horses correlates with neutrophil abundance.. Vet Immunol Immunopathol 2006 Oct 15;113(3-4):267-76.
                  pubmed: 16822550doi: 10.1016/j.vetimm.2006.05.010google scholar: lookup
                38. Loftus JP, Belknap JK, Stankiewicz KM, Black SJ. Laminar xanthine oxidase, superoxide dismutase and catalase activities in the prodromal stage of black-walnut induced equine laminitis.. Equine Vet J 2007 Jan;39(1):48-53.
                  pubmed: 17228595doi: 10.2746/042516406x151320google scholar: lookup
                39. Loftus JP, Black SJ, Pettigrew A, Abrahamsen EJ, Belknap JK. Early laminar events involving endothelial activation in horses with black walnut- induced laminitis.. Am J Vet Res 2007 Nov;68(11):1205-11.
                  pubmed: 17975975doi: 10.2460/ajvr.68.11.1205google scholar: lookup
                40. Ludwig A, Weber C. Transmembrane chemokines: versatile 'special agents' in vascular inflammation.. Thromb Haemost 2007 May;97(5):694-703.
                  pubmed: 17479179
                41. Malemud CJ. Matrix metalloproteinases (MMPs) in health and disease: an overview.. Front Biosci 2006 May 1;11:1696-701.
                  pubmed: 16368548doi: 10.2741/1915google scholar: lookup
                42. Malfait AM, Liu RQ, Ijiri K, Komiya S, Tortorella MD. Inhibition of ADAM-TS4 and ADAM-TS5 prevents aggrecan degradation in osteoarthritic cartilage.. J Biol Chem 2002 Jun 21;277(25):22201-8.
                  pubmed: 11956193doi: 10.1074/jbc.M200431200google scholar: lookup
                43. Monaco S, Sparano V, Gioia M, Sbardella D, Di Pierro D, Marini S, Coletta M. Enzymatic processing of collagen IV by MMP-2 (gelatinase A) affects neutrophil migration and it is modulated by extracatalytic domains.. Protein Sci 2006 Dec;15(12):2805-15.
                  pmc: PMC2242443pubmed: 17088321doi: 10.1110/ps.062430706google scholar: lookup
                44. Moss ML, Lambert MH. Shedding of membrane proteins by ADAM family proteases.. Essays Biochem 2002;38:141-53.
                  pubmed: 12463167doi: 10.1042/bse0380141google scholar: lookup
                45. Mungall BA, Pollitt CC. Zymographic analysis of equine laminitis.. Histochem Cell Biol 1999 Dec;112(6):467-72.
                  pubmed: 10651098doi: 10.1007/s004180050430google scholar: lookup
                46. Nagase H, Kashiwagi M. Aggrecanases and cartilage matrix degradation.. Arthritis Res Ther 2003;5(2):94-103.
                  pmc: PMC165039pubmed: 12718749doi: 10.1186/ar630google scholar: lookup
                47. Nagase H, Visse R, Murphy G. Structure and function of matrix metalloproteinases and TIMPs.. Cardiovasc Res 2006 Feb 15;69(3):562-73.
                  pubmed: 16405877doi: 10.1016/j.cardiores.2005.12.002google scholar: lookup
                48. Noe MC, Natarajan V, Snow SL, Mitchell PG, Lopresti-Morrow L, Reeves LM, Yocum SA, Carty TJ, Barberia JA, Sweeney FJ, Liras JL, Vaughn M, Hardink JR, Hawkins JM, Tokar C. Discovery of 3,3-dimethyl-5-hydroxypipecolic hydroxamate-based inhibitors of aggrecanase and MMP-13.. Bioorg Med Chem Lett 2005 Jun 2;15(11):2808-11.
                  pubmed: 15911259doi: 10.1016/j.bmcl.2005.03.105google scholar: lookup
                49. Noe MC, Natarajan V, Snow SL, Wolf-Gouveia LA, Mitchell PG, Lopresti-Morrow L, Reeves LM, Yocum SA, Otterness I, Bliven MA, Carty TJ, Barberia JT, Sweeney FJ, Liras JL, Vaughn M. Discovery of 3-OH-3-methylpipecolic hydroxamates: potent orally active inhibitors of aggrecanase and MMP-13.. Bioorg Med Chem Lett 2005 Jul 15;15(14):3385-8.
                  pubmed: 15953722doi: 10.1016/j.bmcl.2005.05.037google scholar: lookup
                50. Ortega N, Behonick D, Stickens D, Werb Z. How proteases regulate bone morphogenesis.. Ann N Y Acad Sci 2003 May;995:109-16.
                  pubmed: 12814943doi: 10.1111/j.1749-6632.2003.tb03214.xgoogle scholar: lookup
                51. Planting A, van der Gaast A, Schöffski P, Bartkowski M, Verheij C, Noe D, Ferrante K, Verweij J. A phase I and pharmacologic study of the matrix metalloproteinase inhibitor CP-471,358 in patients with advanced solid tumors.. Cancer Chemother Pharmacol 2005 Feb;55(2):136-42.
                  pubmed: 15592721doi: 10.1007/s00280-004-0905-zgoogle scholar: lookup
                52. Pollitt CC. Basement membrane pathology: a feature of acute equine laminitis.. Equine Vet J 1996 Jan;28(1):38-46.
                  pubmed: 8565952doi: 10.1111/j.2042-3306.1996.tb01588.xgoogle scholar: lookup
                53. Pollitt CC, Daradka M. Equine laminitis basement membrane pathology: loss of type IV collagen, type VII collagen and laminin immunostaining.. Equine Vet J Suppl 1998 Sep;(26):139-44.
                  pubmed: 9932105doi: 10.1111/j.2042-3306.1998.tb05133.xgoogle scholar: lookup
                54. Pollitt CC, Pass MA, Pollitt S. Batimastat (BB-94) inhibits matrix metalloproteinases of equine laminitis.. Equine Vet J Suppl 1998 Sep;(26):119-24.
                  pubmed: 9932102doi: 10.1111/j.2042-3306.1998.tb05130.xgoogle scholar: lookup
                55. Ravanti L, Kähäri VM. Matrix metalloproteinases in wound repair (review).. Int J Mol Med 2000 Oct;6(4):391-407.
                  pubmed: 10998429
                56. Rundhaug JE. Matrix metalloproteinases and angiogenesis.. J Cell Mol Med 2005 Apr-Jun;9(2):267-85.
                  pmc: PMC6740080pubmed: 15963249doi: 10.1111/j.1582-4934.2005.tb00355.xgoogle scholar: lookup
                57. Sahin U, Weskamp G, Kelly K, Zhou HM, Higashiyama S, Peschon J, Hartmann D, Saftig P, Blobel CP. Distinct roles for ADAM10 and ADAM17 in ectodomain shedding of six EGFR ligands.. J Cell Biol 2004 Mar 1;164(5):769-79.
                  pmc: PMC2172154pubmed: 14993236doi: 10.1083/jcb.200307137google scholar: lookup
                58. Schlöndorff J, Blobel CP. Metalloprotease-disintegrins: modular proteins capable of promoting cell-cell interactions and triggering signals by protein-ectodomain shedding.. J Cell Sci 1999 Nov;112 ( Pt 21):3603-17.
                  pubmed: 10523497doi: 10.1242/jcs.112.21.3603google scholar: lookup
                59. Sloet van Oldruitenborgh-Oosterbaan MM. Laminitis in the horse: a review.. Vet Q 1999 Oct;21(4):121-7.
                  pubmed: 10568001doi: 10.1080/01652176.1999.9695006google scholar: lookup
                60. Song RH, Tortorella MD, Malfait AM, Alston JT, Yang Z, Arner EC, Griggs DW. Aggrecan degradation in human articular cartilage explants is mediated by both ADAMTS-4 and ADAMTS-5.. Arthritis Rheum 2007 Feb;56(2):575-85.
                  pubmed: 17265492doi: 10.1002/art.22334google scholar: lookup
                61. Stamenkovic I. Extracellular matrix remodelling: the role of matrix metalloproteinases.. J Pathol 2003 Jul;200(4):448-64.
                  pubmed: 12845612doi: 10.1002/path.1400google scholar: lookup
                62. Stanton H, Ung L, Fosang AJ. The 45 kDa collagen-binding fragment of fibronectin induces matrix metalloproteinase-13 synthesis by chondrocytes and aggrecan degradation by aggrecanases.. Biochem J 2002 May 15;364(Pt 1):181-90.
                  pmc: PMC1222560pubmed: 11988091doi: 10.1042/bj3640181google scholar: lookup
                63. Sugimoto K, Takahashi M, Yamamoto Y, Shimada K, Tanzawa K. Identification of aggrecanase activity in medium of cartilage culture.. J Biochem 1999 Aug;126(2):449-55.
                  pubmed: 10423543doi: 10.1093/oxfordjournals.jbchem.a022471google scholar: lookup
                64. Tanaka S, Hamanishi C, Kikuchi H, Fukuda K. Factors related to degradation of articular cartilage in osteoarthritis: a review.. Semin Arthritis Rheum 1998 Jun;27(6):392-9.
                  pubmed: 9662758doi: 10.1016/s0049-0172(98)80019-xgoogle scholar: lookup
                65. Thomsen ME, Davis EG, Rush BR. Black walnut induced laminitis.. Vet Hum Toxicol 2000 Feb;42(1):8-11.
                  pubmed: 10670077
                66. Tortorella M, Pratta M, Liu RQ, Abbaszade I, Ross H, Burn T, Arner E. The thrombospondin motif of aggrecanase-1 (ADAMTS-4) is critical for aggrecan substrate recognition and cleavage.. J Biol Chem 2000 Aug 18;275(33):25791-7.
                  pubmed: 10827174doi: 10.1074/jbc.M001065200google scholar: lookup
                67. Tortorella MD, Malfait AM, Deccico C, Arner E. The role of ADAM-TS4 (aggrecanase-1) and ADAM-TS5 (aggrecanase-2) in a model of cartilage degradation.. Osteoarthritis Cartilage 2001 Aug;9(6):539-52.
                  pubmed: 11520168doi: 10.1053/joca.2001.0427google scholar: lookup
                68. Uhlinger C. Black walnut toxicosis in ten horses.. J Am Vet Med Assoc 1989 Aug 1;195(3):343-4.
                  pubmed: 2768058
                69. Waguespack RW, Cochran A, Belknap JK. Expression of the cyclooxygenase isoforms in the prodromal stage of black walnut-induced laminitis in horses.. Am J Vet Res 2004 Dec;65(12):1724-9.
                  pubmed: 15631041doi: 10.2460/ajvr.2004.65.1724google scholar: lookup
                70. Waguespack RW, Kemppainen RJ, Cochran A, Lin HC, Belknap JK. Increased expression of MAIL, a cytokine-associated nuclear protein, in the prodromal stage of black walnut-induced laminitis.. Equine Vet J 2004 Apr;36(3):285-91.
                  pubmed: 15147139doi: 10.2746/0425164044877099google scholar: lookup
                71. Werb Z, Chin JR. Extracellular matrix remodeling during morphogenesis.. Ann N Y Acad Sci 1998 Oct 23;857:110-8.
                  pubmed: 9917836doi: 10.1111/j.1749-6632.1998.tb10111.xgoogle scholar: lookup
                72. Wojtowicz-Praga S. Clinical potential of matrix metalloprotease inhibitors.. Drugs R D 1999 Feb;1(2):117-29.
                  pubmed: 10566004doi: 10.2165/00126839-199901020-00001google scholar: lookup
                73. Wolfsberg TG, Straight PD, Gerena RL, Huovila AP, Primakoff P, Myles DG, White JM. ADAM, a widely distributed and developmentally regulated gene family encoding membrane proteins with a disintegrin and metalloprotease domain.. Dev Biol 1995 May;169(1):378-83.
                  pubmed: 7750654doi: 10.1006/dbio.1995.1152google scholar: lookup
                74. Xue M, Le NT, Jackson CJ. Targeting matrix metalloproteases to improve cutaneous wound healing.. Expert Opin Ther Targets 2006 Feb;10(1):143-55.
                  pubmed: 16441234doi: 10.1517/14728222.10.1.143google scholar: lookup

                Citations

                This article has been cited 11 times.
                1. Ding J, Shi M, Wang L, Qi D, Tao Z, Hayat MA, Liu T, Zhang JT, Wang H. Gene Expression of Metalloproteinases and Endogenous Inhibitors in the Lamellae of Dairy Heifers With Oligofructose-Induced Laminitis. Front Vet Sci 2020;7:597827.
                  doi: 10.3389/fvets.2020.597827pubmed: 33426020google scholar: lookup
                2. Li S, Zheng X, Ding M, Tao Z, Zhang J, Zhang N. Change in Proteolytic Profile in Heifers After Oligofructose Overload. Front Vet Sci 2020;7:580375.
                  doi: 10.3389/fvets.2020.580375pubmed: 33392282google scholar: lookup
                3. Cassimeris L, Engiles JB, Galantino-Homer H. Interleukin-17A pathway target genes are upregulated in Equus caballus supporting limb laminitis. PLoS One 2020;15(12):e0232920.
                  doi: 10.1371/journal.pone.0232920pubmed: 33301461google scholar: lookup
                4. de Laat MA, Spence RJ, Sillence MN, Pollitt CC. An investigation of the equine epidermal growth factor system during hyperinsulinemic laminitis. PLoS One 2019;14(12):e0225843.
                  doi: 10.1371/journal.pone.0225843pubmed: 31805097google scholar: lookup
                5. Faramarzi B, Lee D, May K, Dong F. Response to acupuncture treatment in horses with chronic laminitis. Can Vet J 2017 Aug;58(8):823-827.
                  pubmed: 28761187
                6. Menzies-Gow NJ, Wray H, Bailey SR, Harris PA, Elliott J. The effect of tumour necrosis factor-α and insulin on equine digital blood vessel function in vitro. Inflamm Res 2014 Aug;63(8):637-47.
                  doi: 10.1007/s00011-014-0736-2pubmed: 24764104google scholar: lookup
                7. Wang L, Pawlak EA, Johnson PJ, Belknap JK, Eades S, Stack S, Cousin H, Black SJ. Impact of laminitis on the canonical Wnt signaling pathway in basal epithelial cells of the equine digital laminae. PLoS One 2013;8(2):e56025.
                  doi: 10.1371/journal.pone.0056025pubmed: 23405249google scholar: lookup
                8. Wang L, Pawlak E, Johnson PJ, Belknap JK, Alfandari D, Black SJ. Effects of cleavage by a disintegrin and metalloproteinase with thrombospondin motifs-4 on gene expression and protein content of versican and aggrecan in the digital laminae of horses with starch gruel-induced laminitis. Am J Vet Res 2012 Jul;73(7):1047-56.
                  doi: 10.2460/ajvr.73.7.1047pubmed: 22738057google scholar: lookup
                9. Pawlak E, Wang L, Johnson PJ, Nuovo G, Taye A, Belknap JK, Alfandari D, Black SJ. Distribution and processing of a disintegrin and metalloproteinase with thrombospondin motifs-4, aggrecan, versican, and hyaluronan in equine digital laminae. Am J Vet Res 2012 Jul;73(7):1035-46.
                  doi: 10.2460/ajvr.73.7.1035pubmed: 22738056google scholar: lookup
                10. de Figueiredo MM, Bueno VC, Royes ICL, Mattos RC, Bastos HBA, Rechsteiner SF. Protamine1, 2 and Catsper1: sperm quality and fertility indicators in Stallions. Anim Reprod 2025;22(4):e20250040.
                  doi: 10.1590/1984-3143-AR2025-0040pubmed: 41393904google scholar: lookup
                11. Baranwal A, Ahmad SF, Gandham RK, Celus CS, Gaur GK. Gene expression profiling of indigenous Tharparkar and crossbred Vrindavani cattle affected with lameness using PBMC model. Trop Anim Health Prod 2024 Dec 7;56(9):402.
                  doi: 10.1007/s11250-024-04236-zpubmed: 39644418google scholar: lookup
                Subscribe to our newsletter
                Join 99,344 horse owners like you who receive our email updates on horse health and nutrition.