Skip to main content
Top
Published in: Skeletal Radiology 8/2006

01-08-2006 | Scientific Article

In vivo MRI of cartilage pathogenesis in surgical models of osteoarthritis

Authors: Didier Laurent, Elizabeth O’Byrne, James Wasvary, Theodore C. Pellas

Published in: Skeletal Radiology | Issue 8/2006

Login to get access

Abstract

Objective

To examine in vivo time-course changes in macromolecular composition of articular cartilage in two surgical models of osteoarthritis (goat: meniscal transection and cartilage incision; rabbit: medial meniscectomy).

Design

Collagen integrity and proteoglycan (PG) content were evaluated in both models by magnetization transfer (MT) and contrast-enhanced MRI, respectively. The MT rate k m for the exchange process between the bulk water and water bound to collagen was determined as a marker of the collagen network. Local changes in cartilage fixed charge density, i.e., where PGs are depleted, were derived from T1 relaxation maps as obtained after an infusion of Gd(DTPA)2−, a paramagnetic agent.

Results

In the goat model, the MT rate constant k m was significantly higher at 2 weeks post surgery, a possible sign of cartilage swelling, then decreased below baseline values, most likely indicative of disruption in the collagen framework. Meanwhile, post-Gd(DTPA)2− MRI acquisition indicated a significant and sustained loss of PGs. The rabbit model produced milder lesions. Although the difference was non-significant, k m steadily decreased in response to the surgical insult while kinetics of Gd(DTPA)2− uptake, after reaching a peak level at 6 weeks, were back to normal values after 12 weeks.

Conclusion

In the goat model, joint instability and cartilage damage was a permanent trigger for cartilage degeneration producing MRI changes. However, biomechanical stress due to partial medial meniscectomy in knees of mature rabbits produced only mild, focal lesions and PG depletion that was partially reversible. This proof-of-concept study identified MT and T1 parameters as useful surrogate markers in animal models of osteoarthritis.
Literature
1.
go back to reference Buckwalter JA, Lane NE. Aging, sports and osteoarthritis. Sports Med Arthrosc Rev 1996; 4:276–287CrossRef Buckwalter JA, Lane NE. Aging, sports and osteoarthritis. Sports Med Arthrosc Rev 1996; 4:276–287CrossRef
2.
go back to reference Lohmander LS. Articular cartilage and osteoarthritis. The role of molecular markers to monitor breakdown, repair and disease. J Anat 1994; 184:477–492PubMed Lohmander LS. Articular cartilage and osteoarthritis. The role of molecular markers to monitor breakdown, repair and disease. J Anat 1994; 184:477–492PubMed
3.
go back to reference Kempson GE. The mechanical properties of articular cartilage. In: Sokoloff L, editor. The joints and synovial fluid. Vol. II. Academic Press, New York 1980:177–238 Kempson GE. The mechanical properties of articular cartilage. In: Sokoloff L, editor. The joints and synovial fluid. Vol. II. Academic Press, New York 1980:177–238
4.
go back to reference Grushko G, Schneiderman R, Maroudas A. Some biochemical and biophysical parameters for the study of the pathogenesis of osteoarthritis: a comparison between the processes of ageing and degeneration in human hip cartilage. Connect Tiss Res 1989; 19:149–176CrossRef Grushko G, Schneiderman R, Maroudas A. Some biochemical and biophysical parameters for the study of the pathogenesis of osteoarthritis: a comparison between the processes of ageing and degeneration in human hip cartilage. Connect Tiss Res 1989; 19:149–176CrossRef
5.
go back to reference Maroudas A, Wachtel E, Grushko G, Katz EP, Weinberg P. The effect of osmotic and mechanical pressures on water partitioning in articular cartilage. Biochim Biophys Acta 1991; 1073:285–294PubMed Maroudas A, Wachtel E, Grushko G, Katz EP, Weinberg P. The effect of osmotic and mechanical pressures on water partitioning in articular cartilage. Biochim Biophys Acta 1991; 1073:285–294PubMed
6.
go back to reference Bank RA, Soudry M, Maroudas A, Mizrahi J, TeKoppele JM. The increased swelling and instantaneous deformation of osteoarthritic cartilage is highly correlated with collagen degradation. Arthritis Rheum 2000; 43(10):2202–2210PubMedCrossRef Bank RA, Soudry M, Maroudas A, Mizrahi J, TeKoppele JM. The increased swelling and instantaneous deformation of osteoarthritic cartilage is highly correlated with collagen degradation. Arthritis Rheum 2000; 43(10):2202–2210PubMedCrossRef
7.
go back to reference Pessis E, Drape JL, Ravaud P, Chevrot A, Dougados M, Ayral X. Assessment of progression in knee osteoarthritis: results of a 1 year study comparing arthroscopy and MRI. Osteoarthritis Cartilage 2003; 11:361–369PubMedCrossRef Pessis E, Drape JL, Ravaud P, Chevrot A, Dougados M, Ayral X. Assessment of progression in knee osteoarthritis: results of a 1 year study comparing arthroscopy and MRI. Osteoarthritis Cartilage 2003; 11:361–369PubMedCrossRef
8.
go back to reference Bashir A, Gray ML, Burstein D. Gd-DTPA2- as a measure of cartilage degradation. Magn Reson Med 1996; 36:665–673PubMedCrossRef Bashir A, Gray ML, Burstein D. Gd-DTPA2- as a measure of cartilage degradation. Magn Reson Med 1996; 36:665–673PubMedCrossRef
9.
go back to reference Laurent D, Wasvary J, Rudin M, O’Byrne E, Pellas TC. In vivo assessment of macromolecular content in articular cartilage of the goat knee. Magn Reson Med 2003; 49:1037–1046PubMedCrossRef Laurent D, Wasvary J, Rudin M, O’Byrne E, Pellas TC. In vivo assessment of macromolecular content in articular cartilage of the goat knee. Magn Reson Med 2003; 49:1037–1046PubMedCrossRef
10.
go back to reference Laurent D, Wasvary J, Yin J, Rudin M, Pellas TC, O’Byrne E. Quantitative and qualitative assessment of articular cartilage in the goat knee with magnetization transfer imaging. Magn Reson Imag 2001; 19(10):1279–1286CrossRef Laurent D, Wasvary J, Yin J, Rudin M, Pellas TC, O’Byrne E. Quantitative and qualitative assessment of articular cartilage in the goat knee with magnetization transfer imaging. Magn Reson Imag 2001; 19(10):1279–1286CrossRef
11.
go back to reference Farkas T, Bihari-Varga M, Biro T. Thermoanalytical and histological study of intra-articular papain-induced degradation and repair of rabbit cartilage. II. Mature animals. Ann Rheum Dis 1976; 35:23–26PubMedCrossRef Farkas T, Bihari-Varga M, Biro T. Thermoanalytical and histological study of intra-articular papain-induced degradation and repair of rabbit cartilage. II. Mature animals. Ann Rheum Dis 1976; 35:23–26PubMedCrossRef
12.
go back to reference Kitoh Y, Katsuramaki T, Tanaka H, Tanaka M, Kitabayashi N, Kataoka M, Fujimori S, Umemoto J, Namba K. Effect of SL-1010 (sodium hyaluronate with high molecular weight) on experimental osteoarthritis induced by intra-articularly applied papain in rabbits. Folia Pharmacol Japon 1992; 100:67–76CrossRef Kitoh Y, Katsuramaki T, Tanaka H, Tanaka M, Kitabayashi N, Kataoka M, Fujimori S, Umemoto J, Namba K. Effect of SL-1010 (sodium hyaluronate with high molecular weight) on experimental osteoarthritis induced by intra-articularly applied papain in rabbits. Folia Pharmacol Japon 1992; 100:67–76CrossRef
13.
go back to reference Van der Kraan PM, Vitters EL, van Beuningen HM, van der Putte LBA, van der Berg WB. Degenerative knee joint lesions in mice after a single intra-articular collagenase injection. A new model of osteoarthritis. J Exp Pathol 1990; 71:19–31 Van der Kraan PM, Vitters EL, van Beuningen HM, van der Putte LBA, van der Berg WB. Degenerative knee joint lesions in mice after a single intra-articular collagenase injection. A new model of osteoarthritis. J Exp Pathol 1990; 71:19–31
14.
go back to reference Williams JM, Brandt KD. Immobilization ameliorates chemically-induced articular cartilage damage. Arthritis Rheum 1984; 27(2):208–216PubMedCrossRef Williams JM, Brandt KD. Immobilization ameliorates chemically-induced articular cartilage damage. Arthritis Rheum 1984; 27(2):208–216PubMedCrossRef
15.
go back to reference Murphy JM, Boynton RE, Kraus KH, Cole JC, Hunziker EB, Pellas T, O’Byrne E, Barry FP. An experimental model of osteoarthritis in goats. Trans Orthop Res Soc 1999; 24:435 Murphy JM, Boynton RE, Kraus KH, Cole JC, Hunziker EB, Pellas T, O’Byrne E, Barry FP. An experimental model of osteoarthritis in goats. Trans Orthop Res Soc 1999; 24:435
16.
go back to reference Laurent D, Wasvary J, O’Byrne E, Rudin M. In vivo qualitative assessments of articular cartilage in the rabbit knee with high-resolution MRI at 3T. Magn Reson Med 2003; 50:541–549PubMedCrossRef Laurent D, Wasvary J, O’Byrne E, Rudin M. In vivo qualitative assessments of articular cartilage in the rabbit knee with high-resolution MRI at 3T. Magn Reson Med 2003; 50:541–549PubMedCrossRef
17.
go back to reference Moskowitz RW, Davis W, Sammarco J, Martens M, Baker J, Mayor M, Burstein AM, Frankel VH. Experimentally induced degenerative joint lesions following partial meniscectomy in the rabbit. Arthritis Rheum 1973; 16:397–405PubMedCrossRef Moskowitz RW, Davis W, Sammarco J, Martens M, Baker J, Mayor M, Burstein AM, Frankel VH. Experimentally induced degenerative joint lesions following partial meniscectomy in the rabbit. Arthritis Rheum 1973; 16:397–405PubMedCrossRef
18.
go back to reference Axelsson I, Berman I, Pita JC. Proteoglycans from rabbit articular and growth plate cartilage: ultracentrifugation, gel chromatography, and electron microscopy. J Biol Chem 1983; 258:8915–8921PubMed Axelsson I, Berman I, Pita JC. Proteoglycans from rabbit articular and growth plate cartilage: ultracentrifugation, gel chromatography, and electron microscopy. J Biol Chem 1983; 258:8915–8921PubMed
19.
go back to reference Manicourt DH, Pita JC, Candido F, Howell DS. Characterization of the proteoglycans recovered under nondissociative conditions from normal articular cartilage of rabbits and dogs. J Biol Chem 1986; 261(12):5426–5433PubMed Manicourt DH, Pita JC, Candido F, Howell DS. Characterization of the proteoglycans recovered under nondissociative conditions from normal articular cartilage of rabbits and dogs. J Biol Chem 1986; 261(12):5426–5433PubMed
20.
go back to reference Manicourt D, Howell DS, Moskowitz RW, Goldberg V, Malemud C, Pita JC. Application of new techniques to separation of proteoglycan aggregates from normal and destabilized rabbit articular cartilages. Acta Biol Hung 1984; 35:137–142PubMed Manicourt D, Howell DS, Moskowitz RW, Goldberg V, Malemud C, Pita JC. Application of new techniques to separation of proteoglycan aggregates from normal and destabilized rabbit articular cartilages. Acta Biol Hung 1984; 35:137–142PubMed
21.
go back to reference Mehraban F, Kuo SY, Rierra H, Chang C, Moskowitz RW. Prostromelysin and procollagenase are differentially up-regulated in chondrocytes from knees of rabbits with experimental osteoarthritis. Arthritis Rheum 1994; 37:1189–1197PubMedCrossRef Mehraban F, Kuo SY, Rierra H, Chang C, Moskowitz RW. Prostromelysin and procollagenase are differentially up-regulated in chondrocytes from knees of rabbits with experimental osteoarthritis. Arthritis Rheum 1994; 37:1189–1197PubMedCrossRef
22.
go back to reference Mehraban F, Lark MW, Ahmed FN, Xu F, Moskowitz RW. Increased secretion and activity of matrix metalloproteinase-3 in synovial tissues and chondrocytes from experimental osteoarthritis. Osteoarthritis Cartilage 1998; 6:286–294PubMedCrossRef Mehraban F, Lark MW, Ahmed FN, Xu F, Moskowitz RW. Increased secretion and activity of matrix metalloproteinase-3 in synovial tissues and chondrocytes from experimental osteoarthritis. Osteoarthritis Cartilage 1998; 6:286–294PubMedCrossRef
23.
go back to reference Mehraban F, Tindal MH, Profitt MM, Moskowitz RW. Temporal pattern of cysteine endopeptidase (cathepsin B) expression in cartilage and synovia from rabbits with experimental osteoarthritis: gene expression in chondrocytes in response to interleukin-1 and matrix depletion. Ann Rheum Dis 1997; 56:108–115PubMedCrossRef Mehraban F, Tindal MH, Profitt MM, Moskowitz RW. Temporal pattern of cysteine endopeptidase (cathepsin B) expression in cartilage and synovia from rabbits with experimental osteoarthritis: gene expression in chondrocytes in response to interleukin-1 and matrix depletion. Ann Rheum Dis 1997; 56:108–115PubMedCrossRef
24.
go back to reference Tammi M, Saamanen AM, Jauhiainen A, Malminen C, Kiviranta I, Helminen H. Proteoglycan alterations in rabbit knee articular cartilage following physical exercise and immobilization. Connect Tissue Res 1983; 11(1):45–55PubMedCrossRef Tammi M, Saamanen AM, Jauhiainen A, Malminen C, Kiviranta I, Helminen H. Proteoglycan alterations in rabbit knee articular cartilage following physical exercise and immobilization. Connect Tissue Res 1983; 11(1):45–55PubMedCrossRef
25.
go back to reference Armstrong SJ, Read RA, Ghosh P, Wilson DM. Moderate exercise exacerbates the osteoarthritic lesions produced in cartilage by meniscectomy: a morphological study. Osteoarthritis Cartilage 1993; 1:89–96PubMedCrossRef Armstrong SJ, Read RA, Ghosh P, Wilson DM. Moderate exercise exacerbates the osteoarthritic lesions produced in cartilage by meniscectomy: a morphological study. Osteoarthritis Cartilage 1993; 1:89–96PubMedCrossRef
26.
go back to reference Stanisz GJ, Henkelman RM. Gd-DTPA relaxivity depends on macromolecular content. Magn Reson Med 2000; 44:665–667PubMedCrossRef Stanisz GJ, Henkelman RM. Gd-DTPA relaxivity depends on macromolecular content. Magn Reson Med 2000; 44:665–667PubMedCrossRef
27.
go back to reference Wayne JS, Kraft KA, Shields KJ, Yin C, Owen JR, Disler DG. MR imaging of normal and matrix-depleted cartilage: correlation with biomechanical function and biochemical composition. Radiology 2003; 228(2):493–499PubMedCrossRef Wayne JS, Kraft KA, Shields KJ, Yin C, Owen JR, Disler DG. MR imaging of normal and matrix-depleted cartilage: correlation with biomechanical function and biochemical composition. Radiology 2003; 228(2):493–499PubMedCrossRef
28.
go back to reference Gillis A, Gray M, Burstein D. Relaxivity of gadolinium agents in cartilage. Magn Res Med 2002; 48:1068–1071CrossRef Gillis A, Gray M, Burstein D. Relaxivity of gadolinium agents in cartilage. Magn Res Med 2002; 48:1068–1071CrossRef
29.
go back to reference Bashir A, Nieminen M, Williams A, Burstein D. T1 of cartilage with Gd-DTPA(2-) and GdHPDO3A: Implications for dGEMRIC imaging. Proc Intl Soc Magn Reson Med, Kyoto, Japan, 2004; 11:818 Bashir A, Nieminen M, Williams A, Burstein D. T1 of cartilage with Gd-DTPA(2-) and GdHPDO3A: Implications for dGEMRIC imaging. Proc Intl Soc Magn Reson Med, Kyoto, Japan, 2004; 11:818
30.
go back to reference Otterness IG, Swindell AC, Zimmerer RO, Poole AR, Ionescu M, Weiner E. An analysis of 14 molecular markers for monitoring osteoarthritis: segregation of the markers into clusters and distinguishing osteoarthritis at baseline. Osteoarthritis Cartilage 2000; 8:180–185PubMedCrossRef Otterness IG, Swindell AC, Zimmerer RO, Poole AR, Ionescu M, Weiner E. An analysis of 14 molecular markers for monitoring osteoarthritis: segregation of the markers into clusters and distinguishing osteoarthritis at baseline. Osteoarthritis Cartilage 2000; 8:180–185PubMedCrossRef
Metadata
Title
In vivo MRI of cartilage pathogenesis in surgical models of osteoarthritis
Authors
Didier Laurent
Elizabeth O’Byrne
James Wasvary
Theodore C. Pellas
Publication date
01-08-2006
Publisher
Springer-Verlag
Published in
Skeletal Radiology / Issue 8/2006
Print ISSN: 0364-2348
Electronic ISSN: 1432-2161
DOI
https://doi.org/10.1007/s00256-006-0133-1

Other articles of this Issue 8/2006

Skeletal Radiology 8/2006 Go to the issue