J Knee Surg 2015; 28(02): 175-182
DOI: 10.1055/s-0034-1376333
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Characterization of Knee Meniscal Pathology: Correlation of Gross, Histologic, Biochemical, Molecular, and Radiographic Measures of Disease

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

Publication History

14 January 2014

06 March 2014

Publication Date:
07 May 2014 (online)

Abstract

Meniscal pathology is an extremely prevalent problem, which inevitably leads to osteoarthritis and associated pain, swelling, and disability. Relatively little data are available regarding the molecular, biochemical, and histologic aspects of meniscal disease. This study characterizes meniscal pathology in the presence of symptomatic osteoarthritis and correlates clinical and basic science data in an attempt to delineate clinically relevant mechanisms of disease. Twenty-seven knees from 23 patients who underwent total knee arthroplasty comprised the affected group and 6 aged nonsymptomatic knees were used as controls. All meniscal tissues were harvested and subjectively scored for gross and histologic pathology. Biochemical analyses were performed to determine glycosaminoglycan (GAG) content, collagen (hydroxyproline) content, and water content. Real-time polymerase chain reaction analysis was conducted for genes involved in synthesis (collagens [col] 1, 2, 3, and 6), degradation (matrix metalloproteinases [MMP-1, -2, -3, -13]), and angiogenesis (vascular endothelial growth factor). Weight-bearing, anterior-posterior radiographic views were used to determine joint space measurements for lateral and medial compartments, and were subjectively scored for osteoarthritic changes. Data were compared for statistically significant differences and to determine the presence and strength of correlations among variables assessed. Affected menisci had significantly higher gross and histologic pathology scores compared with control menisci. Affected menisci had significantly higher water, proteoglycan, and collagen content compared with control menisci. Col 1, 3, and 6 gene expression levels for the affected group were significantly increased compared with controls. MMP-13 expression was significantly increased for the affected group. MMP-2 and -3 expression levels were significantly lower in the affected group compared with controls. The affected group had significantly more joint space narrowing and higher radiographic scores for medial compared with lateral compartments. Several strong and moderately strong correlations were present between variables. These data suggest that in vitro measures of meniscal pathology have potential value for understanding disease mechanisms and predicting clinical disease.

 
  • References

  • 1 Medical Data International, Newport Beach, CA, USA, September 2003
  • 2 Fithian DC, Kelly MA, Mow VC. Material properties and structure-function relationships in the menisci. Clin Orthop Relat Res 1990; 252 (252) 19-31
  • 3 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
  • 4 Bonneux I, Vandekerckhove B. Arthroscopic partial lateral meniscectomy long-term results in athletes. Acta Orthop Belg 2002; 68 (4) 356-361
  • 5 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
  • 6 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
  • 7 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
  • 8 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
  • 9 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
  • 10 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
  • 11 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
  • 12 Cook JL. The current status of treatment for large meniscal defects. Clin Orthop Relat Res 2005; 435 (435) 88-95
  • 13 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
  • 14 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
  • 15 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
  • 16 Farndale RW, Buttle DJ, Barrett AJ. Improved quantitation and discrimination of sulphated glycosaminoglycans by use of dimethylmethylene blue. Biochim Biophys Acta 1986; 883 (2) 173-177
  • 17 Reddy GK, Enwemeka CS. A simplified method for the analysis of hydroxyproline in biological tissues. Clin Biochem 1996; 29 (3) 225-229
  • 18 Freed LE, Hollander AP, Martin I, Barry JR, Langer R, Vunjak-Novakovic G. Chondrogenesis in a cell-polymer-bioreactor system. Exp Cell Res 1998; 240 (1) 58-65
  • 19 Tognana E, Chen F, Padera RF , et al. Adjacent tissues (cartilage, bone) affect the functional integration of engineered calf cartilage in vitro. Osteoarthritis Cartilage 2005; 13 (2) 129-138
  • 20 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
  • 21 Muller PY, Janovjak H, Miserez AR, Dobbie Z. Processing of gene expression data generated by quantitative real-time RT-PCR. Biotechniques 2002; 32 (6) 1372-1374 , 1376, 1378–1379
  • 22 Vignon E, Piperno M, Le Graverand MPH , et al. Measurement of radiographic joint space width in the tibiofemoral compartment of the osteoarthritic knee: comparison of standing anteroposterior and Lyon schuss views. Arthritis Rheum 2003; 48 (2) 378-384
  • 23 Duryea J, Zaim S, Genant HK. New radiographic-based surrogate outcome measures for osteoarthritis of the knee. Osteoarthritis Cartilage 2003; 11 (2) 102-110
  • 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
  • 25 Vignon E, Conrozier T, Piperno M, Richard S, Carrillon Y, Fantino O. Radiographic assessment of hip and knee osteoarthritis. Recommendations: recommended guidelines. Osteoarthritis Cartilage 1999; 7 (4) 434-436
  • 26 Kellgren JH, Lawrence JS. Radiological assessment of osteo-arthrosis. Ann Rheum Dis 1957; 16 (4) 494-502
  • 27 Englund M, Roos EM, Lohmander LS. Impact of type of meniscal tear on radiographic and symptomatic knee osteoarthritis: a sixteen-year followup of meniscectomy with matched controls. Arthritis Rheum 2003; 48 (8) 2178-2187
  • 28 Hunter DJ, Zhang YQ, Tu X , et al. Change in joint space width: hyaline articular cartilage loss or alteration in meniscus?. Arthritis Rheum 2006; 54 (8) 2488-2495
  • 29 Englund M, Guermazi A, Gale D , et al. Incidental meniscal findings on knee MRI in middle-aged and elderly persons. N Engl J Med 2008; 359 (11) 1108-1115
  • 30 Greis PE, Bardana DD, Holmstrom MC, Burks RT. Meniscal injury: I. Basic science and evaluation. J Am Acad Orthop Surg 2002; 10 (3) 168-176
  • 31 Baker BE, Peckham AC, Pupparo F, Sanborn JC. Review of meniscal injury and associated sports. Am J Sports Med 1985; 13 (1) 1-4
  • 32 Widuchowski W, Widuchowski J, Trzaska T. Articular cartilage defects: study of 25,124 knee arthroscopies. Knee 2007; 14 (3) 177-182
  • 33 Swank M, Stulberg SD, Jiganti J, Machairas S. The natural history of unicompartmental arthroplasty. An eight-year follow-up study with survivorship analysis. Clin Orthop Relat Res 1993; 286 (286) 130-142
  • 34 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
  • 35 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
  • 36 Adams ME, Billingham MEJ, Muir H. The glycosaminoglycans in menisci in experimental and natural osteoarthritis. Arthritis Rheum 1983; 26 (1) 69-76
  • 37 Ghosh P, Taylor TKF. The knee joint meniscus. A fibrocartilage of some distinction. Clin Orthop Relat Res 1987; 224 (224) 52-63
  • 38 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
  • 39 Syal M, Goyal N, Nagi ON , et al. Immunohistochemistry of osteoarthritic meniscus in man. Bull Postgrad Inst Med Educ Res Chandigarh 2007; 41: 11-16
  • 40 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
  • 41 Ishihara G, Kojima T, Saito Y, Ishiguro N. Roles of metalloproteinase-3 and aggrecanase 1 and 2 in aggrecan cleavage during human meniscus degeneration. Orthop Rev (Pavia) 2009; 1 (2) e14
  • 42 Wang Y, Yang L, Zhang J , et al. Differential MMP-2 activity induced by mechanical compression and inflammatory factors in human synoviocytes. Mol Cell Biomech 2010; 7 (2) 105-114
  • 43 Tsushima H, Okazaki K, Hayashida M, Ushijima T, Iwamoto Y. CCAAT/enhancer binding protein β regulates expression of matrix metalloproteinase-3 in arthritis. Ann Rheum Dis 2012; 71 (1) 99-107
  • 44 Leeman MF, Curran S, Murray GI. The structure, regulation, and function of human matrix metalloproteinase-13. Crit Rev Biochem Mol Biol 2002; 37 (3) 149-166
  • 45 Katsuragawa Y, Saitoh K, Tanaka N , et al. Changes of human menisci in osteoarthritic knee joints. Osteoarthritis Cartilage 2010; 18 (9) 1133-1143
  • 46 Roller BL, Stoker AM, Marberry KM , et al. Characterization of meniscal pathology with molecular and proteomic analyses. Paper Presented at: 56th Annual Meeting of the Orthopaedic Research Society; March 6–9, 2010, New Orleans, LA
  • 47 Stoker AM, Garner BC, Roller BL. Comparison and correlation of in vitro cytokine production by osteoarthritic cartilage, meniscus, and synovium. Paper Presented at: 56th Annual Meeting of the Orthopaedic Research Society; March 6–9, 2010, New Orleans, LA
  • 48 Stoker AM, Garner BC, Roller BL. Comparison and correlation of synovial fluid cytokine levels and in vitro cytokine production by osteoarthritic cartilage, meniscus, and synovium. Paper Presented at: 56th Annual Meeting of the Orthopaedic Research Society; March 6–9, 2010, New Orleans, LA
  • 49 Bhattacharyya T, Gale D, Dewire P , et al. The clinical importance of meniscal tears demonstrated by magnetic resonance imaging in osteoarthritis of the knee. J Bone Joint Surg Am 2003; 85-A (1) 4-9
  • 50 Englund M, Roemer FW, Hayashi D, Crema MD, Guermazi A. Meniscus pathology, osteoarthritis and the treatment controversy. Nat Rev Rheumatol 2012; 8 (7) 412-419
  • 51 Herrlin S, Hållander M, Wange P, Weidenhielm L, Werner S. Arthroscopic or conservative treatment of degenerative medial meniscal tears: a prospective randomised trial. Knee Surg Sports Traumatol Arthrosc 2007; 15 (4) 393-401
  • 52 Herrlin SV, Wange PO, Lapidus G, Hållander M, Werner S, Weidenhielm L. Is arthroscopic surgery beneficial in treating non-traumatic, degenerative medial meniscal tears? A five year follow-up. Knee Surg Sports Traumatol Arthrosc 2013; 21 (2) 358-364