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J Knee Surg 2015; 28(06): 496-505
DOI: 10.1055/s-0034-1394164
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Characterization of Meniscal Pathology Using Molecular and Proteomic Analyses

Brandon L. Roller
1   Arthrex, Inc., Naples, Florida
2   Comparative Orthopaedic Laboratory, University of Missouri, Columbia, Missouri
,
Farrah Monibi
2   Comparative Orthopaedic Laboratory, University of Missouri, Columbia, Missouri
,
Aaron M. Stoker
2   Comparative Orthopaedic Laboratory, University of Missouri, Columbia, Missouri
,
B. Sonny Bal
3   Department of Orthopaedic Surgery, University of Missouri, Columbia, Missouri
,
James P. Stannard
3   Department of Orthopaedic Surgery, University of Missouri, Columbia, Missouri
,
James L. Cook
2   Comparative Orthopaedic Laboratory, University of Missouri, Columbia, Missouri
3   Department of Orthopaedic Surgery, University of Missouri, Columbia, Missouri
› Author Affiliations
Further Information

Publication History

07 February 2014

18 August 2014

Publication Date:
23 October 2014 (online)

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Abstract

The meniscus is a complex tissue and is integral to knee joint health and function. Although the meniscus has been studied for years, a relatively large amount of basic science data on meniscal health and disease are unavailable. Genomic and proteomic analyses of meniscal pathology could greatly improve our understanding of etiopathogenesis and the progression of meniscal disease, yet these analyses are lacking in the current literature. Therefore, the objective of this study was to use microarray and proteomic analyses to compare aged-normal and pathologic meniscal tissues. Meniscal tissue was collected from the knees of five patient groups (n = 3/group). Cohorts included patients undergoing meniscectomy with or without articular cartilage pathology, patients undergoing total knee arthroplasty with mild or moderate–severe osteoarthritis, and aged-normal controls from organ donors. Tissue sections were collected from the white/white and white/red zones of posterior medial menisci. Expression levels were compared between pathologic and control menisci to identify genes of interest (at least a ×1.5 fold change in expression levels between two or more groups) using microarray analysis. Proteomics analysis was performed using mass spectrometry to identify proteins of interest (those with possible trends identified between the aged-normal and pathologic groups). The microarray identified 157 genes of interest. Genes were categorized into the following subgroups: (1) synthesis, (2) vascularity, (3) degradation and antidegradation, and (4) signaling pathways. Mass spectrometry identified 173 proteins of interest. Proteins were further divided into the following categories: (1) extracellular matrix (ECM) proteins; (2) proteins associated with vascularity; (3) degradation and antidegradation proteins; (4) cytoskeleton proteins; (5) glycolysis pathway proteins; and (6) signaling proteins. These data provide novel molecular and biochemical information for the investigation of meniscal pathology. Further evaluation of these disease indicators will help researchers develop algorithms for diagnostic, therapeutic, and prognostic strategies related to meniscal disorders.

Keywords

meniscus - pathology - osteoarthritis - knee - biomarker
 

  • References

  • 1 Walker PS, Erkman MJ. The role of the menisci in force transmission across the knee. Clin Orthop Relat Res 1975; (109) 184-192
    PubMedGoogle Scholar
  • 2 Ghosh P, Taylor TK. The knee joint meniscus. A fibrocartilage of some distinction. Clin Orthop Relat Res 1987; (224) 52-63
    PubMedGoogle Scholar
  • 3 Setton LA, Guilak F, Hsu EW, Vail TP. Biomechanical factors in tissue engineered meniscal repair. Clin Orthop Relat Res 1999; ;(367, Suppl): S254-S272
    PubMedGoogle Scholar
  • 4 Medical Data International. Newport Beach, CA; September 2003
    PubMedGoogle Scholar
  • 5 Fithian DC, Kelly MA, Mow VC. Material properties and structure-function relationships in the menisci. Clin Orthop Relat Res 1990; 252 (252) 19-31
    PubMedGoogle Scholar
  • 6 Andersson-Molina H, Karlsson H, Rockborn P. Arthroscopic partial and total meniscectomy: A long-term follow-up study with matched controls. Arthroscopy 2002; 18 (2) 183-189
    CrossrefPubMedGoogle Scholar
  • 7 Bonneux I, Vandekerckhove B. Arthroscopic partial lateral meniscectomy long-term results in athletes. Acta Orthop Belg 2002; 68 (4) 356-361
    PubMedGoogle Scholar
  • 8 Chatain F, Robinson AHN, Adeleine P, Chambat P, Neyret P. The natural history of the knee following arthroscopic medial meniscectomy. Knee Surg Sports Traumatol Arthrosc 2001; 9 (1) 15-18
    CrossrefPubMedGoogle Scholar
  • 9 Cicuttini FM, Forbes A, Yuanyuan W, Rush G, Stuckey SL. Rate of knee cartilage loss after partial meniscectomy. J Rheumatol 2002; 29 (9) 1954-1956
    PubMedGoogle Scholar
  • 10 McKinley TO, English DK, Bay BK. Trabecular bone strain changes resulting from partial and complete meniscectomy. Clin Orthop Relat Res 2003; 407 (407) 259-267
    CrossrefPubMedGoogle Scholar
  • 11 van Tienen TG, Heijkants RG, de Groot JH , et al. Presence and mechanism of knee articular cartilage degeneration after meniscal reconstruction in dogs. Osteoarthritis Cartilage 2003; 11 (1) 78-84
    CrossrefPubMedGoogle Scholar
  • 12 Wyland DJ, Guilak F, Elliott DM, Setton LA, Vail TP. Chondropathy after meniscal tear or partial meniscectomy in a canine model. J Orthop Res 2002; 20 (5) 996-1002
    CrossrefPubMedGoogle Scholar
  • 13 Cook JL. The current status of treatment for large meniscal defects. Clin Orthop Relat Res 2005; 435 (435) 88-95
    PubMedGoogle Scholar
  • 14 Cook JL, Fox DB, Malaviya P , et al. Evaluation of small intestinal submucosa grafts for meniscal regeneration in a clinically relevant posterior meniscectomy model in dogs. J Knee Surg 2006; 19 (3) 159-167
    Article in Thieme ConnectPubMedGoogle Scholar
  • 15 Cook JL, Fox DB, Malaviya P , et al. Long-term outcome for large meniscal defects treated with small intestinal submucosa in a dog model. Am J Sports Med 2006; 34 (1) 32-42
    CrossrefPubMedGoogle Scholar
  • 16 Ochi K, Daigo Y, Katagiri T , et al. Expression profiles of two types of human knee-joint cartilage. J Hum Genet 2003; 48 (4) 177-182
    CrossrefPubMedGoogle Scholar
  • 17 Önnerfjord P, Khabut A, Reinholt FP, Svensson O, Heinegård D. Quantitative proteomic analysis of eight cartilaginous tissues reveals characteristic differences as well as similarities between subgroups. J Biol Chem 2012; 287 (23) 18913-18924
    CrossrefPubMedGoogle Scholar
  • 18 Sun Y, Mauerhan DR, Honeycutt PR , et al. Calcium deposition in osteoarthritic meniscus and meniscal cell culture. Arthritis Res Ther 2010; 12 (2) R56
    CrossrefPubMedGoogle Scholar
  • 19 Loeser RF, Olex AL, McNulty MA , et al. Microarray analysis reveals age-related differences in gene expression during the development of osteoarthritis in mice. Arthritis Rheum 2012; 64 (3) 705-717
    CrossrefPubMedGoogle Scholar
  • 20 Burleigh A, Chanalaris A, Gardiner MD , et al. Joint immobilization prevents murine osteoarthritis and reveals the highly mechanosensitive nature of protease expression in vivo. Arthritis Rheum 2012; 64 (7) 2278-2288
    CrossrefPubMedGoogle Scholar
  • 21 Roller BL, Monibi FA, Stoker AM, Kuroki K, Bal BS, Cook JL. Characterization of knee meniscal pathology: correlation of gross, histologic, biochemical, molecular, and radiographic measures of disease. J Knee Surg 2014; May 7 (Epub ahead of print); doi: 10.1055/s-0034-1376333
    PubMedGoogle Scholar
  • 22 Brittberg M, Peterson L. Introduction of an articular cartilage classification. ICRS Newsletter 1998; 1: 5-8
    PubMedGoogle Scholar
  • 23 Brittberg M, Winalski CS. Evaluation of cartilage injuries and repair. J Bone Joint Surg Am 2003; 85-A (Suppl. 02) 58-69
    PubMedGoogle Scholar
  • 24 Scott Jr WW, Lethbridge-Cejku M, Reichle R, Wigley FM, Tobin JD, Hochberg MC. Reliability of grading scales for individual radiographic features of osteoarthritis of the knee. The Baltimore longitudinal study of aging atlas of knee osteoarthritis. Invest Radiol 1993; 28 (6) 497-501
    CrossrefPubMedGoogle Scholar
  • 25 Schramm M, Falkai P, Tepest R , et al. Stability of RNA transcripts in post-mortem psychiatric brains. J Neural Transm 1999; 106 (3-4) 329-335
    CrossrefPubMedGoogle Scholar
  • 26 Yasojima K, McGeer EG, McGeer PL. High stability of mRNAs postmortem and protocols for their assessment by RT-PCR. Brain Res Brain Res Protoc 2001; 8 (3) 212-218
    CrossrefPubMedGoogle Scholar
  • 27 Kuliwaba JS, Fazzalari NL, Findlay DM. Stability of RNA isolated from human trabecular bone at post-mortem and surgery. Biochim Biophys Acta 2005; 1740 (1) 1-11
    CrossrefPubMedGoogle Scholar
  • 28 Reno C, Marchuk L, Sciore P, Frank CB, Hart DA. Rapid isolation of total RNA from small samples of hypocellular, dense connective tissues. Biotechniques 1997; 22 (6) 1082-1086
    PubMedGoogle Scholar
  • 29 Hellio Le Graverand MP, Vignon E, Otterness IG, Hart DA. Early changes in lapine menisci during osteoarthritis development: Part I: cellular and matrix alterations. Osteoarthritis Cartilage 2001; 9 (1) 56-64
    CrossrefPubMedGoogle Scholar
  • 30 Herwig J, Egner E, Buddecke E. Chemical changes of human knee joint menisci in various stages of degeneration. Ann Rheum Dis 1984; 43 (4) 635-640
    CrossrefPubMedGoogle Scholar
  • 31 Adams ME, Billingham MEJ, Muir H. The glycosaminoglycans in menisci in experimental and natural osteoarthritis. Arthritis Rheum 1983; 26 (1) 69-76
    CrossrefPubMedGoogle Scholar
  • 32 Sun Y, Mauerhan DR. Meniscal calcification, pathogenesis and implications. Curr Opin Rheumatol 2012; 24 (2) 152-157
    CrossrefPubMedGoogle Scholar
  • 33 Pauli C, Grogan SP, Patil S , et al. Macroscopic and histopathologic analysis of human knee menisci in aging and osteoarthritis. Osteoarthritis Cartilage 2011; 19 (9) 1132-1141
    CrossrefPubMedGoogle Scholar
  • 34 Bray RC, Smith JA, Eng MK, Leonard CA, Sutherland CA, Salo PT. Vascular response of the meniscus to injury: effects of immobilization. J Orthop Res 2001; 19 (3) 384-390
    CrossrefPubMedGoogle Scholar
  • 35 Ashraf S, Wibberley H, Mapp PI, Hill R, Wilson D, Walsh DA. Increased vascular penetration and nerve growth in the meniscus: a potential source of pain in osteoarthritis. Ann Rheum Dis 2011; 70 (3) 523-529
    CrossrefPubMedGoogle Scholar
  • 36 Maurer LM, Tomasini-Johansson BR, Mosher DF. Emerging roles of fibronectin in thrombosis. Thromb Res 2010; 125 (4) 287-291
    CrossrefPubMedGoogle Scholar
  • 37 Johnson A, Smith R, Saxne T, Hickery M, Heinegård D. Fibronectin fragments cause release and degradation of collagen-binding molecules from equine explant cultures. Osteoarthritis Cartilage 2004; 12 (2) 149-159
    CrossrefPubMedGoogle Scholar
  • 38 Schwarzbauer JE. Alternative splicing of fibronectin: three variants, three functions. BioEssays 1991; 13 (10) 527-533
    CrossrefPubMedGoogle Scholar
  • 39 Matsuda M. Fibronectin—its functions and roles in tissue repair [in Japanese]. Nippon Geka Gakkai Zasshi 1984; 85 (9) 882-886
    PubMedGoogle Scholar
  • 40 Mosher DF, Schad PE. Cross-linking of fibronectin to collagen by blood coagulation Factor XIIIa. J Clin Invest 1979; 64 (3) 781-787
    CrossrefPubMedGoogle Scholar
  • 41 Monboisse JC, Borel JP. Oxidative damage to collagen. EXS 1992; 62: 323-327
    PubMedGoogle Scholar
  • 42 McCord JM. Free radicals and inflammation: protection of synovial fluid by superoxide dismutase. Science 1974; 185 (4150) 529-531
    CrossrefPubMedGoogle Scholar
  • 43 Regan E, Flannelly J, Bowler R , et al. Extracellular superoxide dismutase and oxidant damage in osteoarthritis. Arthritis Rheum 2005; 52 (11) 3479-3491
    CrossrefPubMedGoogle Scholar
  • 44 Hellio Le Graverand MP, Sciore P, Eggerer J , et al. Formation and phenotype of cell clusters in osteoarthritic meniscus. Arthritis Rheum 2001; 44 (8) 1808-1818
    CrossrefPubMedGoogle Scholar
  • 45 Gandhi R, Takahashi M, Virtanen C, Syed K, Davey JR, Mahomed NN. Microarray analysis of the infrapatellar fat pad in knee osteoarthritis: relationship with joint inflammation. J Rheumatol 2011; 38 (9) 1966-1972
    CrossrefPubMedGoogle Scholar