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Journal of proteomics2011; 74(5); 704-715; doi: 10.1016/j.jprot.2011.02.017

High throughput proteomic analysis of the secretome in an explant model of articular cartilage inflammation.

Abstract: This study employed a targeted high-throughput proteomic approach to identify the major proteins present in the secretome of articular cartilage. Explants from equine metacarpophalangeal joints were incubated alone or with interleukin-1beta (IL-1β, 10ng/ml), with or without carprofen, a non-steroidal anti-inflammatory drug, for six days. After tryptic digestion of culture medium supernatants, resulting peptides were separated by HPLC and detected in a Bruker amaZon ion trap instrument. The five most abundant peptides in each MS scan were fragmented and the fragmentation patterns compared to mammalian entries in the Swiss-Prot database, using the Mascot search engine. Tryptic peptides originating from aggrecan core protein, cartilage oligomeric matrix protein (COMP), fibronectin, fibromodulin, thrombospondin-1 (TSP-1), clusterin (CLU), cartilage intermediate layer protein-1 (CILP-1), chondroadherin (CHAD) and matrix metalloproteinases MMP-1 and MMP-3 were detected. Quantitative western blotting confirmed the presence of CILP-1, CLU, MMP-1, MMP-3 and TSP-1. Treatment with IL-1β increased MMP-1, MMP-3 and TSP-1 and decreased the CLU precursor but did not affect CILP-1 and CLU levels. Many of the proteins identified have well-established extracellular matrix functions and are involved in early repair/stress responses in cartilage. This high throughput approach may be used to study the changes that occur in the early stages of osteoarthritis.
Copyright © 2011 Elsevier B.V. All rights reserved.
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Publication Date: 2011-02-24 PubMed ID: 21354348PubMed Central: PMC3078332DOI: 10.1016/j.jprot.2011.02.017Google 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.

This research project used advanced proteomic techniques to identify the main proteins present in the secretome of articular cartilage under different conditions, and considered implications for understanding early stages of osteoarthritis.

Experimental Design

  • The researchers extracted explants from equine metacarpophalangeal joints. An explant refers to a tissue sample that has been removed from the body of an organism and kept alive in an artificial environment for experimental purposes.
  • The explants were then subjected to different conditions: (i) incubated alone, (ii) with the pro-inflammatory cytokine, interleukin-1beta (IL-1β), or (iii) with IL-1β in the presence of carprofen, a non-steroidal anti-inflammatory drug. Carprofen is employed here to evaluate its effect on the secretome under inflammatory conditions.

Proteomic Analysis

  • The culture medium supernatants (liquid part above the settled cells) were sampled and subjected to a specific protease (trypsin) digestion, breaking down the proteins into smaller peptide fragments.
  • These peptides were then separated by High-Performance Liquid Chromatography (HPLC), a method commonly used to separate components of a mixture, and detected using an ion trap instrument (specifically a Bruker amaZon model). Ion trap is a type of mass spectrometer that uses electric or magnetic fields to trap charged particles.
  • The most abundant peptides in each Mass Spectrometry (MS) scan were fragmented further and their patterns compared with mammalian entries in the Swiss-Prot database, a manually curated protein sequence database. The search engine Mascot was employed for this comparison.

Major Findings

  • Peptides derived from several proteins including aggrecan core protein, cartilage oligomeric matrix protein (COMP), fibronectin, fibromodulin and others were found. These are important structural proteins in the cartilage’s extracellular matrix.
  • Quantitative western blotting, a technique that enables detection and measurement of specific proteins, confirmed the presence of several proteins including CILP-1, CLU, MMP-1, MMP-3, and TSP-1.
  • Under inflammatory conditions (interleukin-1beta exposure), the levels of certain proteins (MMP-1, MMP-3, TSP-1) increased, while the precursor for CLU decreased. These proteins are generally involved in cartilage degradation and matrix remodelling processes, which are prominent factors in osteoarthritis development.

Conclusion

  • The findings give significant insight into the proteins active in the inflammatory response of articular cartilage. Understanding these proteins can be instrumental in studying early stages of osteoarthritis, giving potential possibilities for earlier diagnosis and intervention strategies.

Cite This Article

APA
Clutterbuck AL, Smith JR, Allaway D, Harris P, Liddell S, Mobasheri A. (2011). High throughput proteomic analysis of the secretome in an explant model of articular cartilage inflammation. J Proteomics, 74(5), 704-715. https://doi.org/10.1016/j.jprot.2011.02.017

Publication

Journal of proteomics
ISSN: 1876-7737
NlmUniqueID: 101475056
Country: Netherlands
Language: English
Volume: 74
Issue: 5
Pages: 704-715

Researcher Affiliations

Clutterbuck, Abigail L
  • Musculoskeletal Research Group, Division of Veterinary Medicine, School of Veterinary Medicine and Science, Faculty of Medicine and Health Sciences, University of Nottingham, Leicestershire, United Kingdom.
Smith, Julia R
    Allaway, David
      Harris, Pat
        Liddell, Susan
          Mobasheri, Ali

            MeSH Terms

            • Animals
            • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
            • Carbazoles / pharmacology
            • Cartilage, Articular / metabolism
            • Cartilage, Articular / pathology
            • Gene Expression Regulation
            • Horses
            • Inflammation / drug therapy
            • Inflammation / metabolism
            • Inflammation / pathology
            • Models, Biological
            • Osteochondritis / drug therapy
            • Osteochondritis / metabolism
            • Osteochondritis / pathology
            • Proteome / metabolism

            Grant Funding

            • BBS/S/M/2006/13141 / Biotechnology and Biological Sciences Research Council

            References

            This article includes 71 references
            1. Buckwalter JA, Mankin HJ, Grodzinsky AJ. Articular cartilage and osteoarthritis.. Instr Course Lect 2005;54:465-80.
              pubmed: 15952258
            2. Buckwalter JA, Mankin HJ. Articular cartilage: tissue design and chondrocyte-matrix interactions.. Instr Course Lect 1998;47:477-86.
              pubmed: 9571449
            3. Eyre DR. Collagens and cartilage matrix homeostasis.. Clin Orthop Relat Res 2004 Oct;(427 Suppl):S118-22.
              pubmed: 15480053doi: 10.1097/01.blo.0000144855.48640.b9google scholar: lookup
            4. Kuettner KE. Biochemistry of articular cartilage in health and disease.. Clin Biochem 1992 Jun;25(3):155-63.
              pubmed: 1633629doi: 10.1016/0009-9120(92)90224-ggoogle scholar: lookup
            5. Hardingham TE, Fosang AJ. Proteoglycans: many forms and many functions.. FASEB J 1992 Feb 1;6(3):861-70.
              pubmed: 1740236
            6. Feng H, Danfelter M, Strömqvist B, Heinegård D. Extracellular matrix in disc degeneration.. J Bone Joint Surg Am 2006 Apr;88 Suppl 2:25-9.
              pubmed: 16595439doi: 10.2106/JBJS.E.01341google scholar: lookup
            7. Archer CW, Francis-West P. The chondrocyte.. Int J Biochem Cell Biol 2003 Apr;35(4):401-4.
              pubmed: 12565700doi: 10.1016/s1357-2725(02)00301-1google scholar: lookup
            8. Goldring MB, Marcu KB. Cartilage homeostasis in health and rheumatic diseases.. Arthritis Res Ther 2009;11(3):224.
              pmc: PMC2714092pubmed: 19519926doi: 10.1186/ar2592google scholar: lookup
            9. Aigner T, Soeder S, Haag J. IL-1beta and BMPs--interactive players of cartilage matrix degradation and regeneration.. Eur Cell Mater 2006 Oct 26;12:49-56; discussion 56.
              pubmed: 17068722doi: 10.22203/ecm.v012a06google scholar: lookup
            10. Goldring MB, Goldring SR. Osteoarthritis.. J Cell Physiol 2007 Dec;213(3):626-34.
              pubmed: 17786965doi: 10.1002/jcp.21258google scholar: lookup
            11. Samuels J, Krasnokutsky S, Abramson SB. Osteoarthritis: a tale of three tissues.. Bull NYU Hosp Jt Dis 2008;66(3):244-50.
              pubmed: 18937640
            12. Felson DT. An update on the pathogenesis and epidemiology of osteoarthritis.. Radiol Clin North Am 2004 Jan;42(1):1-9, v.
              pubmed: 15049520doi: 10.1016/S0033-8389(03)00161-1google scholar: lookup
            13. Okada Y, Shinmei M, Tanaka O, Naka K, Kimura A, Nakanishi I, Bayliss MT, Iwata K, Nagase H. Localization of matrix metalloproteinase 3 (stromelysin) in osteoarthritic cartilage and synovium.. Lab Invest 1992 Jun;66(6):680-90.
              pubmed: 1602738
            14. Goldring SR, Goldring MB. The role of cytokines in cartilage matrix degeneration in osteoarthritis.. Clin Orthop Relat Res 2004 Oct;(427 Suppl):S27-36.
              pubmed: 15480070doi: 10.1097/01.blo.0000144854.66565.8fgoogle scholar: lookup
            15. Goldring MB, Berenbaum F. The regulation of chondrocyte function by proinflammatory mediators: prostaglandins and nitric oxide.. Clin Orthop Relat Res 2004 Oct;(427 Suppl):S37-46.
              pubmed: 15480072doi: 10.1097/01.blo.0000144484.69656.e4google scholar: lookup
            16. Aigner T, Vornehm SI, Zeiler G, Dudhia J, von der Mark K, Bayliss MT. Suppression of cartilage matrix gene expression in upper zone chondrocytes of osteoarthritic cartilage.. Arthritis Rheum 1997 Mar;40(3):562-9.
              pubmed: 9082945doi: 10.1002/art.1780400323google scholar: lookup
            17. Clark AG, Jordan JM, Vilim V, Renner JB, Dragomir AD, Luta G, Kraus VB. Serum cartilage oligomeric matrix protein reflects osteoarthritis presence and severity: the Johnston County Osteoarthritis Project.. Arthritis Rheum 1999 Nov;42(11):2356-64.
              pubmed: 10555031doi: 10.1002/1529-0131(199911)42:11<2356::AID-ANR14>3.0.CO;2-Rgoogle scholar: lookup
            18. Rousseau JC, Delmas PD. Biological markers in osteoarthritis.. Nat Clin Pract Rheumatol 2007 Jun;3(6):346-56.
              pubmed: 17538566doi: 10.1038/ncprheum0508google scholar: lookup
            19. Williams FM. Biomarkers: in combination they may do better.. Arthritis Res Ther 2009;11(5):130.
              pmc: PMC2787279pubmed: 19886980doi: 10.1186/ar2839google scholar: lookup
            20. Polacek M, Bruun JA, Johansen O, Martinez I. Differences in the secretome of cartilage explants and cultured chondrocytes unveiled by SILAC technology.. J Orthop Res 2010 Aug;28(8):1040-9.
              pubmed: 20108312doi: 10.1002/jor.21067google scholar: lookup
            21. Ruiz-Romero C, Calamia V, Carreira V, Mateos J, Fernández P, Blanco FJ. Strategies to optimize two-dimensional gel electrophoresis analysis of the human joint proteome.. Talanta 2010 Feb 15;80(4):1552-60.
              pubmed: 20082814doi: 10.1016/j.talanta.2009.05.022google scholar: lookup
            22. Ruiz-Romero C, López-Armada MJ, Blanco FJ. Proteomic characterization of human normal articular chondrocytes: a novel tool for the study of osteoarthritis and other rheumatic diseases.. Proteomics 2005 Aug;5(12):3048-59.
              pubmed: 16035116doi: 10.1002/pmic.200402106google scholar: lookup
            23. Ruiz-Romero C, Blanco FJ. Proteomics role in the search for improved diagnosis, prognosis and treatment of osteoarthritis.. Osteoarthritis Cartilage 2010 Apr;18(4):500-9.
              pubmed: 20060947doi: 10.1016/j.joca.2009.11.012google scholar: lookup
            24. Wu J, Liu W, Bemis A, Wang E, Qiu Y, Morris EA, Flannery CR, Yang Z. Comparative proteomic characterization of articular cartilage tissue from normal donors and patients with osteoarthritis.. Arthritis Rheum 2007 Nov;56(11):3675-84.
              pubmed: 17968891doi: 10.1002/art.22876google scholar: lookup
            25. Wilson R, Belluoccio D, Little CB, Fosang AJ, Bateman JF. Proteomic characterization of mouse cartilage degradation in vitro.. Arthritis Rheum 2008 Oct;58(10):3120-31.
              pubmed: 18821673doi: 10.1002/art.23789google scholar: lookup
            26. Wilson R, Belluoccio D, Little CB, Fosang AJ, Bateman JF. Proteomic characterization of mouse cartilage degradation in vitro.. Arthritis Rheum 2008 Oct;58(10):3120-31.
              pubmed: 18821673doi: 10.1002/art.23789google scholar: lookup
            27. Cillero-Pastor B, Ruiz-Romero C, Caramés B, López-Armada MJ, Blanco FJ. Proteomic analysis by two-dimensional electrophoresis to identify the normal human chondrocyte proteome stimulated by tumor necrosis factor alpha and interleukin-1beta.. Arthritis Rheum 2010 Mar;62(3):802-14.
              pubmed: 20131227doi: 10.1002/art.27265google scholar: lookup
            28. Stevens AL, Wishnok JS, Chai DH, Grodzinsky AJ, Tannenbaum SR. A sodium dodecyl sulfate-polyacrylamide gel electrophoresis-liquid chromatography tandem mass spectrometry analysis of bovine cartilage tissue response to mechanical compression injury and the inflammatory cytokines tumor necrosis factor alpha and interleukin-1beta.. Arthritis Rheum 2008 Feb;58(2):489-500.
              pubmed: 18240213doi: 10.1002/art.23120google scholar: lookup
            29. Li H, Yang HS, Wu TJ, Zhang XY, Jiang WH, Ma QL, Chen YX, Xu Y, Li S, Hua ZC. Proteomic analysis of early-response to mechanical stress in neonatal rat mandibular condylar chondrocytes.. J Cell Physiol 2010 Jun;223(3):610-22.
              pubmed: 20127708doi: 10.1002/jcp.22052google scholar: lookup
            30. Zhang WB, Wang L. Label-free quantitative proteome analysis of skeletal tissues under mechanical load.. J Cell Biochem 2009 Oct 15;108(3):600-11.
              pubmed: 19670388doi: 10.1002/jcb.22291google scholar: lookup
            31. Perkins DN, Pappin DJ, Creasy DM, Cottrell JS. Probability-based protein identification by searching sequence databases using mass spectrometry data.. Electrophoresis 1999 Dec;20(18):3551-67.
              pubmed: 10612281doi: 10.1002/(SICI)1522-2683(19991201)20:18<3551::AID-ELPS3551>3.0.CO;2-2google scholar: lookup
            32. Vizcaíno JA, Côté R, Reisinger F, Foster JM, Mueller M, Rameseder J, Hermjakob H, Martens L. A guide to the Proteomics Identifications Database proteomics data repository.. Proteomics 2009 Sep;9(18):4276-83.
              pmc: PMC2970915pubmed: 19662629doi: 10.1002/pmic.200900402google scholar: lookup
            33. Barsnes H, Vizcaíno JA, Eidhammer I, Martens L. PRIDE Converter: making proteomics data-sharing easy.. Nat Biotechnol 2009 Jul;27(7):598-9.
              pubmed: 19587657doi: 10.1038/nbt0709-598google scholar: lookup
            34. Lester PJ, Hubbard SJ. Comparative bioinformatic analysis of complete proteomes and protein parameters for cross-species identification in proteomics.. Proteomics 2002 Oct;2(10):1392-405.
              pubmed: 12422356doi: 10.1002/1615-9861(200210)2:10<1392::AID-PROT1392>3.0.CO;2-Lgoogle scholar: lookup
            35. Liska AJ, Shevchenko A. Expanding the organismal scope of proteomics: cross-species protein identification by mass spectrometry and its implications.. Proteomics 2003 Jan;3(1):19-28.
              pubmed: 12548630doi: 10.1002/pmic.200390004google scholar: lookup
            36. Chamrad DC, Koerting G, Gobom J, Thiele H, Klose J, Meyer HE, Blueggel M. Interpretation of mass spectrometry data for high-throughput proteomics.. Anal Bioanal Chem 2003 Aug;376(7):1014-22.
              pubmed: 12845399doi: 10.1007/s00216-003-1995-xgoogle scholar: lookup
            37. Clutterbuck AL, Mobasheri A, Shakibaei M, Allaway D, Harris P. Interleukin-1beta-induced extracellular matrix degradation and glycosaminoglycan release is inhibited by curcumin in an explant model of cartilage inflammation.. Ann N Y Acad Sci 2009 Aug;1171:428-35.
              pubmed: 19723086doi: 10.1111/j.1749-6632.2009.04687.xgoogle scholar: lookup
            38. DiCesare PE, Mörgelin M, Mann K, Paulsson M. Cartilage oligomeric matrix protein and thrombospondin 1. Purification from articular cartilage, electron microscopic structure, and chondrocyte binding.. Eur J Biochem 1994 Aug 1;223(3):927-37.
              pubmed: 8055970doi: 10.1111/j.1432-1033.1994.tb19070.xgoogle scholar: lookup
            39. Rosenberg K, Olsson H, Mörgelin M, Heinegård D. Cartilage oligomeric matrix protein shows high affinity zinc-dependent interaction with triple helical collagen.. J Biol Chem 1998 Aug 7;273(32):20397-403.
              pubmed: 9685393doi: 10.1074/jbc.273.32.20397google scholar: lookup
            40. Lohmander LS, Saxne T, Heinegård DK. Release of cartilage oligomeric matrix protein (COMP) into joint fluid after knee injury and in osteoarthritis.. Ann Rheum Dis 1994 Jan;53(1):8-13.
              pmc: PMC1005235pubmed: 8311563doi: 10.1136/ard.53.1.8google scholar: lookup
            41. Misumi K, Tagami M, Kamimura T, Miyakoshi D, Helal IE, Arai K, Fujiki M. Urine cartilage oligomeric matrix protein (COMP) measurement is useful in discriminating the osteoarthritic Thoroughbreds.. Osteoarthritis Cartilage 2006 Nov;14(11):1174-80.
              pubmed: 16895759doi: 10.1016/j.joca.2006.04.017google scholar: lookup
            42. Arai K, Misumi K, Carter SD, Shinbara S, Fujiki M, Sakamoto H. Analysis of cartilage oligomeric matrix protein (COMP) degradation and synthesis in equine joint disease.. Equine Vet J 2005 Jan;37(1):31-6.
              pubmed: 15651731doi: 10.2746/0425164054406784google scholar: lookup
            43. Petersson IF, Boegård T, Dahlström J, Svensson B, Heinegård D, Saxne T. Bone scan and serum markers of bone and cartilage in patients with knee pain and osteoarthritis.. Osteoarthritis Cartilage 1998 Jan;6(1):33-9.
              pubmed: 9616437doi: 10.1053/joca.1997.0090google scholar: lookup
            44. Tseng S, Reddi AH, Di Cesare PE. Cartilage Oligomeric Matrix Protein (COMP): A Biomarker of Arthritis.. Biomark Insights 2009 Feb 17;4:33-44.
              pmc: PMC2716683pubmed: 19652761doi: 10.4137/bmi.s645google scholar: lookup
            45. Brama PA, TeKoppele JM, Beekman B, van El B, Barneveld A, van Weeren PR. Influence of development and joint pathology on stromelysin enzyme activity in equine synovial fluid.. Ann Rheum Dis 2000 Feb;59(2):155-7.
              pmc: PMC1753061pubmed: 10666176doi: 10.1136/ard.59.2.155google scholar: lookup
            46. Tung JT, Fenton JI, Arnold C, Alexander L, Yuzbasiyan-Gurkan V, Venta PJ, Peters TL, Orth MW, Richardson DW, Caron JP. Recombinant equine interleukin-1beta induces putative mediators of articular cartilage degradation in equine chondrocytes.. Can J Vet Res 2002 Jan;66(1):19-25.
              pmc: PMC226977pubmed: 11858644
            47. Sadowski T, Steinmeyer J. Effects of non-steroidal antiinflammatory drugs and dexamethasone on the activity and expression of matrix metalloproteinase-1, matrix metalloproteinase-3 and tissue inhibitor of metalloproteinases-1 by bovine articular chondrocytes.. Osteoarthritis Cartilage 2001 Jul;9(5):407-15.
              pubmed: 11467888doi: 10.1053/joca.2000.0406google scholar: lookup
            48. Lawler J, Hynes RO. The structure of human thrombospondin, an adhesive glycoprotein with multiple calcium-binding sites and homologies with several different proteins.. J Cell Biol 1986 Nov;103(5):1635-48.
              pmc: PMC2114380pubmed: 2430973doi: 10.1083/jcb.103.5.1635google scholar: lookup
            49. Chen H, Herndon ME, Lawler J. The cell biology of thrombospondin-1.. Matrix Biol 2000 Dec;19(7):597-614.
              pubmed: 11102749doi: 10.1016/s0945-053x(00)00107-4google scholar: lookup
            50. Pfander D, Cramer T, Deuerling D, Weseloh G, Swoboda B. Expression of thrombospondin-1 and its receptor CD36 in human osteoarthritic cartilage.. Ann Rheum Dis 2000 Jun;59(6):448-54.
              pmc: PMC1753153pubmed: 10834862doi: 10.1136/ard.59.6.448google scholar: lookup
            51. Petrak J, Ivanek R, Toman O, Cmejla R, Cmejlova J, Vyoral D, Zivny J, Vulpe CD. Déjà vu in proteomics. A hit parade of repeatedly identified differentially expressed proteins.. Proteomics 2008 May;8(9):1744-9.
              pubmed: 18442176doi: 10.1002/pmic.200700919google scholar: lookup
            52. Wang P, Bouwman FG, Mariman EC. Generally detected proteins in comparative proteomics--a matter of cellular stress response?. Proteomics 2009 Jun;9(11):2955-66.
              pubmed: 19415655doi: 10.1002/pmic.200800826google scholar: lookup
            53. Kraus VB. Biomarkers in osteoarthritis.. Curr Opin Rheumatol 2005 Sep;17(5):641-6.
              pubmed: 16093846doi: 10.1097/01.bor.0000174195.15421.17google scholar: lookup
            54. Mobasheri A, Henrotin Y. Identification, validation and qualification of biomarkers for osteoarthritis in humans and companion animals: mission for the next decade.. Vet J 2010 Aug;185(2):95-7.
              pubmed: 20554463doi: 10.1016/j.tvjl.2010.05.026google scholar: lookup
            55. Vossenaar ER, Després N, Lapointe E, van der Heijden A, Lora M, Senshu T, van Venrooij WJ, Ménard HA. Rheumatoid arthritis specific anti-Sa antibodies target citrullinated vimentin.. Arthritis Res Ther 2004;6(2):R142-50.
              pmc: PMC400433pubmed: 15059278doi: 10.1186/ar1149google scholar: lookup
            56. Suzuki A, Yamada R, Chang X, Tokuhiro S, Sawada T, Suzuki M, Nagasaki M, Nakayama-Hamada M, Kawaida R, Ono M, Ohtsuki M, Furukawa H, Yoshino S, Yukioka M, Tohma S, Matsubara T, Wakitani S, Teshima R, Nishioka Y, Sekine A, Iida A, Takahashi A, Tsunoda T, Nakamura Y, Yamamoto K. Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis.. Nat Genet 2003 Aug;34(4):395-402.
              pubmed: 12833157doi: 10.1038/ng1206google scholar: lookup
            57. Harris ML, Darrah E, Lam GK, Bartlett SJ, Giles JT, Grant AV, Gao P, Scott WW Jr, El-Gabalawy H, Casciola-Rosen L, Barnes KC, Bathon JM, Rosen A. Association of autoimmunity to peptidyl arginine deiminase type 4 with genotype and disease severity in rheumatoid arthritis.. Arthritis Rheum 2008 Jul;58(7):1958-67.
              pmc: PMC2692635pubmed: 18576335doi: 10.1002/art.23596google scholar: lookup
            58. Kolfenbach JR, Deane KD, Derber LA, O'Donnell CI, Gilliland WR, Edison JD, Rosen A, Darrah E, Norris JM, Holers VM. Autoimmunity to peptidyl arginine deiminase type 4 precedes clinical onset of rheumatoid arthritis.. Arthritis Rheum 2010 Sep;62(9):2633-9.
              pmc: PMC2946499pubmed: 20496417doi: 10.1002/art.27570google scholar: lookup
            59. Auger I, Martin M, Balandraud N, Roudier J. Rheumatoid arthritis-specific autoantibodies to peptidyl arginine deiminase type 4 inhibit citrullination of fibrinogen.. Arthritis Rheum 2010 Jan;62(1):126-31.
              pubmed: 20039406doi: 10.1002/art.27230google scholar: lookup
            60. Tirumalai RS, Chan KC, Prieto DA, Issaq HJ, Conrads TP, Veenstra TD. Characterization of the low molecular weight human serum proteome.. Mol Cell Proteomics 2003 Oct;2(10):1096-103.
              pubmed: 12917320doi: 10.1074/mcp.M300031-MCP200google scholar: lookup
            61. Shores KS, Knapp DR. Assessment approach for evaluating high abundance protein depletion methods for cerebrospinal fluid (CSF) proteomic analysis.. J Proteome Res 2007 Sep;6(9):3739-51.
              pubmed: 17696521doi: 10.1021/pr070293wgoogle scholar: lookup
            62. Zwickl H, Traxler E, Staettner S, Parzefall W, Grasl-Kraupp B, Karner J, Schulte-Hermann R, Gerner C. A novel technique to specifically analyze the secretome of cells and tissues.. Electrophoresis 2005 Jul;26(14):2779-85.
              pubmed: 15966010doi: 10.1002/elps.200410387google scholar: lookup
            63. Guo D, Tan W, Wang F, Lv Z, Hu J, Lv T, Chen Q, Gu X, Wan B, Zhang Z. Proteomic analysis of human articular cartilage: identification of differentially expressed proteins in knee osteoarthritis.. Joint Bone Spine 2008 Jul;75(4):439-44.
              pubmed: 18468937doi: 10.1016/j.jbspin.2007.12.003google scholar: lookup
            64. Ruiz-Romero C, Carreira V, Rego I, Remeseiro S, López-Armada MJ, Blanco FJ. Proteomic analysis of human osteoarthritic chondrocytes reveals protein changes in stress and glycolysis.. Proteomics 2008 Feb;8(3):495-507.
              pubmed: 18186017doi: 10.1002/pmic.200700249google scholar: lookup
            65. Gobezie R, Kho A, Krastins B, Sarracino DA, Thornhill TS, Chase M, Millett PJ, Lee DM. High abundance synovial fluid proteome: distinct profiles in health and osteoarthritis.. Arthritis Res Ther 2007;9(2):R36.
              pmc: PMC1906814pubmed: 17407561doi: 10.1186/ar2172google scholar: lookup
            66. Bo GP, Zhou LN, He WF, Luo GX, Jia XF, Gan CJ, Chen GX, Fang YF, Larsen PM, Wu J. Analyses of differential proteome of human synovial fibroblasts obtained from arthritis.. Clin Rheumatol 2009 Feb;28(2):191-9.
              pubmed: 18807103doi: 10.1007/s10067-008-1013-ygoogle scholar: lookup
            67. Didangelos A, Yin X, Mandal K, Baumert M, Jahangiri M, Mayr M. Proteomics characterization of extracellular space components in the human aorta.. Mol Cell Proteomics 2010 Sep;9(9):2048-62.
              pmc: PMC2938114pubmed: 20551380doi: 10.1074/mcp.M110.001693google scholar: lookup
            68. Nie L, Wu G, Culley DE, Scholten JC, Zhang W. Integrative analysis of transcriptomic and proteomic data: challenges, solutions and applications.. Crit Rev Biotechnol 2007 Apr-Jun;27(2):63-75.
              pubmed: 17578703doi: 10.1080/07388550701334212google scholar: lookup
            69. Connor JR, Kumar S, Sathe G, Mooney J, O'Brien SP, Mui P, Murdock PR, Gowen M, Lark MW. Clusterin expression in adult human normal and osteoarthritic articular cartilage.. Osteoarthritis Cartilage 2001 Nov;9(8):727-37.
              pubmed: 11795992doi: 10.1053/joca.2001.0475google scholar: lookup
            70. von der Mark K, Gauss V, von der Mark H, Müller P. Relationship between cell shape and type of collagen synthesised as chondrocytes lose their cartilage phenotype in culture.. Nature 1977 Jun 9;267(5611):531-2.
              pubmed: 559947doi: 10.1038/267531a0google scholar: lookup
            71. Quinn TM, Grodzinsky AJ, Hunziker EB, Sandy JD. Effects of injurious compression on matrix turnover around individual cells in calf articular cartilage explants.. J Orthop Res 1998 Jul;16(4):490-9.
              pubmed: 9747792doi: 10.1002/jor.1100160415google scholar: lookup

            Citations

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            1. Wakale S, Wu X, Sonar Y, Sun A, Fan X, Crawford R, Prasadam I. How are Aging and Osteoarthritis Related?. Aging Dis 2023 Jun 1;14(3):592-604.
              doi: 10.14336/AD.2022.0831pubmed: 37191424google scholar: lookup
            2. Kovács P, Pushparaj PN, Takács R, Mobasheri A, Matta C. The clusterin connectome: Emerging players in chondrocyte biology and putative exploratory biomarkers of osteoarthritis. Front Immunol 2023;14:1103097.
              doi: 10.3389/fimmu.2023.1103097pubmed: 37033956google scholar: lookup
            3. Dechêne L, Colin M, Demazy C, Fransolet M, Niesten A, Arnould T, Serteyn D, Dieu M, Renard P. Characterization of the Proteins Secreted by Equine Muscle-Derived Mesenchymal Stem Cells Exposed to Cartilage Explants in Osteoarthritis Model. Stem Cell Rev Rep 2023 Feb;19(2):550-567.
              doi: 10.1007/s12015-022-10463-4pubmed: 36271312google scholar: lookup
            4. Liu Y, Zhang Z, Li T, Xu H, Zhang H. Senescence in osteoarthritis: from mechanism to potential treatment. Arthritis Res Ther 2022 Jul 22;24(1):174.
              doi: 10.1186/s13075-022-02859-xpubmed: 35869508google scholar: lookup
            5. Kalvaityte U, Matta C, Bernotiene E, Pushparaj PN, Kiapour AM, Mobasheri A. Exploring the translational potential of clusterin as a biomarker of early osteoarthritis. J Orthop Translat 2022 Jan;32:77-84.
              doi: 10.1016/j.jot.2021.10.001pubmed: 34976733google scholar: lookup
            6. Khella CM, Asgarian R, Horvath JM, Rolauffs B, Hart ML. An Evidence-Based Systematic Review of Human Knee Post-Traumatic Osteoarthritis (PTOA): Timeline of Clinical Presentation and Disease Markers, Comparison of Knee Joint PTOA Models and Early Disease Implications. Int J Mol Sci 2021 Feb 17;22(4).
              doi: 10.3390/ijms22041996pubmed: 33671471google scholar: lookup
            7. Liu L, He J, Liu C, Yang M, Fu J, Yi J, Ai X, Liu M, Zhuang Y, Zhang Y, Huang B, Li C, Zhou Y, Feng C. Cartilage intermediate layer protein affects the progression of intervertebral disc degeneration by regulating the extracellular microenvironment (Review). Int J Mol Med 2021 Feb;47(2):475-484.
              doi: 10.3892/ijmm.2020.4832pubmed: 33416131google scholar: lookup
            8. Arabiyat AS, Chen H, Erndt-Marino J, Burkhard K, Scola L, Fleck A, Wan LQ, Hahn MS. Hyperosmolar Ionic Solutions Modulate Inflammatory Phenotype and sGAG Loss in a Cartilage Explant Model. Cartilage 2021 Dec;13(2_suppl):713S-721S.
              doi: 10.1177/1947603520961167pubmed: 32975437google scholar: lookup
            9. Miran I, Scherer D, Ostyn P, Mazouni C, Drusch F, Bernard M, Louvet E, Adam J, Mathieu MC, Haffa M, Antignac JP, Le Bizec B, Vielh P, Dessen P, Perdry H, Delaloge S, Feunteun J. Adipose Tissue Properties in Tumor-Bearing Breasts. Front Oncol 2020;10:1506.
              doi: 10.3389/fonc.2020.01506pubmed: 32974182google scholar: lookup
            10. Jeremiasse B, Matta C, Fellows CR, Boocock DJ, Smith JR, Liddell S, Lafeber F, van Spil WE, Mobasheri A. Alterations in the chondrocyte surfaceome in response to pro-inflammatory cytokines. BMC Mol Cell Biol 2020 Jun 26;21(1):47.
              doi: 10.1186/s12860-020-00288-9pubmed: 32586320google scholar: lookup
            11. Song P, Kwon Y, Joo JY, Kim DG, Yoon JH. Secretomics to Discover Regulators in Diseases. Int J Mol Sci 2019 Aug 9;20(16).
              doi: 10.3390/ijms20163893pubmed: 31405033google scholar: lookup
            12. Fernández-Puente P, González-Rodríguez L, Calamia V, Picchi F, Lourido L, Camacho-Encina M, Oreiro N, Rocha B, Paz-González R, Marina A, García C, Blanco FJ, Ruiz-Romero C. Analysis of Endogenous Peptides Released from Osteoarthritic Cartilage Unravels Novel Pathogenic Markers. Mol Cell Proteomics 2019 Oct;18(10):2018-2028.
              doi: 10.1074/mcp.RA119.001554pubmed: 31352363google scholar: lookup
            13. Rezuș E, Cardoneanu A, Burlui A, Luca A, Codreanu C, Tamba BI, Stanciu GD, Dima N, Bădescu C, Rezuș C. The Link Between Inflammaging and Degenerative Joint Diseases. Int J Mol Sci 2019 Jan 31;20(3).
              doi: 10.3390/ijms20030614pubmed: 30708978google scholar: lookup
            14. Schneider MC, Barnes CA, Bryant SJ. Characterization of the chondrocyte secretome in photoclickable poly(ethylene glycol) hydrogels. Biotechnol Bioeng 2017 Sep;114(9):2096-2108.
              doi: 10.1002/bit.26320pubmed: 28436002google scholar: lookup
            15. Greene MA, Loeser RF. Aging-related inflammation in osteoarthritis. Osteoarthritis Cartilage 2015 Nov;23(11):1966-71.
              doi: 10.1016/j.joca.2015.01.008pubmed: 26521742google scholar: lookup
            16. Veronesi F, Fini M, Giavaresi G, Ongaro A, De Mattei M, Pellati A, Setti S, Tschon M. Experimentally induced cartilage degeneration treated by pulsed electromagnetic field stimulation; an in vitro study on bovine cartilage. BMC Musculoskelet Disord 2015 Oct 20;16:308.
              doi: 10.1186/s12891-015-0760-6pubmed: 26480822google scholar: lookup
            17. Pu X, Oxford JT. Proteomic Analysis of Engineered Cartilage. Methods Mol Biol 2015;1340:263-78.
              doi: 10.1007/978-1-4939-2938-2_19pubmed: 26445845google scholar: lookup
            18. Swan AL, Stekel DJ, Hodgman C, Allaway D, Alqahtani MH, Mobasheri A, Bacardit J. A machine learning heuristic to identify biologically relevant and minimal biomarker panels from omics data. BMC Genomics 2015;16 Suppl 1(Suppl 1):S2.
              doi: 10.1186/1471-2164-16-S1-S2pubmed: 25923811google scholar: lookup
            19. Xu J, Zhang C, Song W. Screening of differentially expressed genes associated with non-union skeletal fractures and analysis with a DNA microarray. Exp Ther Med 2014 Mar;7(3):609-614.
              doi: 10.3892/etm.2014.1478pubmed: 24520254google scholar: lookup
            20. Bundgaard L, Jacobsen S, Sørensen MA, Sun Z, Deutsch EW, Moritz RL, Bendixen E. The Equine PeptideAtlas: a resource for developing proteomics-based veterinary research. Proteomics 2014 Mar;14(6):763-73.
              doi: 10.1002/pmic.201300398pubmed: 24436130google scholar: lookup
            21. Williams A, Smith JR, Allaway D, Harris P, Liddell S, Mobasheri A. Carprofen inhibits the release of matrix metalloproteinases 1, 3, and 13 in the secretome of an explant model of articular cartilage stimulated with interleukin 1β. Arthritis Res Ther 2013;15(6):R223.
              doi: 10.1186/ar4424pubmed: 24373218google scholar: lookup
            22. Swan AL, Hillier KL, Smith JR, Allaway D, Liddell S, Bacardit J, Mobasheri A. Analysis of mass spectrometry data from the secretome of an explant model of articular cartilage exposed to pro-inflammatory and anti-inflammatory stimuli using machine learning. BMC Musculoskelet Disord 2013 Dec 13;14:349.
              doi: 10.1186/1471-2474-14-349pubmed: 24330474google scholar: lookup
            23. Peffers MJ, Beynon RJ, Clegg PD. Absolute quantification of selected proteins in the human osteoarthritic secretome. Int J Mol Sci 2013 Oct 15;14(10):20658-81.
              doi: 10.3390/ijms141020658pubmed: 24132152google scholar: lookup
            24. Furse S, Liddell S, Ortori CA, Williams H, Neylon DC, Scott DJ, Barrett DA, Gray DA. The lipidome and proteome of oil bodies from Helianthus annuus (common sunflower). J Chem Biol 2013 Apr;6(2):63-76.
              doi: 10.1007/s12154-012-0090-1pubmed: 23532185google scholar: lookup
            25. Loeser RF. Aging processes and the development of osteoarthritis. Curr Opin Rheumatol 2013 Jan;25(1):108-13.
              doi: 10.1097/BOR.0b013e32835a9428pubmed: 23080227google scholar: lookup
            26. Calamia V, Lourido L, Fernández-Puente P, Mateos J, Rocha B, Montell E, Vergés J, Ruiz-Romero C, Blanco FJ. Secretome analysis of chondroitin sulfate-treated chondrocytes reveals anti-angiogenic, anti-inflammatory and anti-catabolic properties. Arthritis Res Ther 2012 Oct 2;14(5):R202.
              doi: 10.1186/ar4040pubmed: 23031212google scholar: lookup
            27. Brown KJ, Formolo CA, Seol H, Marathi RL, Duguez S, An E, Pillai D, Nazarian J, Rood BR, Hathout Y. Advances in the proteomic investigation of the cell secretome. Expert Rev Proteomics 2012 Jun;9(3):337-45.
              doi: 10.1586/epr.12.21pubmed: 22809211google scholar: lookup
            28. Gharbi M, Deberg M, Henrotin Y. Application for proteomic techniques in studying osteoarthritis: a review. Front Physiol 2011;2:90.
              doi: 10.3389/fphys.2011.00090pubmed: 22144964google scholar: lookup
            29. Leite CBG, Bumberger A, Merkely G, Maietta K, Wright EK, Borg-Stein J, Charles JF, Jacobs CA, Lattermann C. Specialized pro-resolving mediators alleviate inflammation and cartilage breakdown in vitro and may play a pivotal role in platelet-rich plasma. Sci Rep 2025 Oct 7;15(1):34977.
              doi: 10.1038/s41598-025-18933-8pubmed: 41057538google scholar: lookup
            30. Smith MM, Melrose J. COMP Is a Biomarker of Cartilage Destruction, Extracellular Matrix and Vascular Remodeling and Tissue Repair. Int J Mol Sci 2025 Sep 19;26(18).
              doi: 10.3390/ijms26189182pubmed: 41009743google scholar: lookup
            31. Shah YY, Partain BD, Aldrich JL, Strinden M, Dobson J, Rinaldi-Ramos C, Allen KD. Proteomic characterization of particle-protein coronas shows differences between osteoarthritic and contralateral knees in a rat model. Connect Tissue Res 2025 Jan;66(1):59-72.
              doi: 10.1080/03008207.2025.2459242pubmed: 39988892google scholar: lookup
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