• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of amjpatholAmerican Journal of Pathology For AuthorsAmerican Journal of Pathology SubscribeAmerican Journal of Pathology SearchAmerican Journal of Pathology Current IssueAmerican Journal of Pathology About the JournalAmerican Journal of Pathology
Am J Pathol. Dec 1989; 135(6): 1001–1014.
PMCID: PMC1880494

Development of osteoarthritic lesions in mice by "metabolic" and "mechanical" alterations in the knee joints.

Abstract

Male, 10-week-old C57B1 10 mice received a single intraarticular injection in the knee joints with papain, iodoacetate, or collagenase. This led to osteoarthritic lesions, such as matrix depletion, chondrocyte proliferation, and osteophyte formation, in the injected knee joints within several weeks. After injection of iodoacetate and papain, the main osteoarthritic alterations were localized in the femoropatellar joint, whereas injection of collagenase led to marked osteoarthritic lesions in the femorotibial joint. The mechanism of induction of these alterations appears to differ for iodoacetate and papain on one site and collagenase on the other site. Data are presented that collagenase injection, by way of damaging ligaments and tendons, destabilizes the knee joint eventually leading to osteoarthritic alterations. In contrast, injection of papain or iodoacetate directly interferes with cartilage metabolism resulting in osteoarthritic changes.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (3.8M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • le Riche W Harding. Planning Your Retirement. The Complete Canadian Self-Help Guide. CMAJ. 1986 May 15;134(10):b1160–1160. [PMC free article]
  • Peyron JG. Osteoarthritis. The epidemiologic viewpoint. Clin Orthop Relat Res. 1986 Dec;(213):13–19. [PubMed]
  • Brocklehurst R, Bayliss MT, Maroudas A, Coysh HL, Freeman MA, Revell PA, Ali SY. The composition of normal and osteoarthritic articular cartilage from human knee joints. With special reference to unicompartmental replacement and osteotomy of the knee. J Bone Joint Surg Am. 1984 Jan;66(1):95–106. [PubMed]
  • Rostand KS, Baker JR, Caterson B, Christner JE. Articular cartilage proteoglycans from normal and osteoarthritic mice. Arthritis Rheum. 1986 Jan;29(1):95–105. [PubMed]
  • Moskowitz RW, Howell DS, Goldberg VM, Muniz O, Pita JC. Cartilage proteoglycan alterations in an experimentally induced model of rabbit osteoarthritis. Arthritis Rheum. 1979 Feb;22(2):155–163. [PubMed]
  • Mankin HJ, Dorfman H, Lippiello L, Zarins A. Biochemical and metabolic abnormalities in articular cartilage from osteo-arthritic human hips. II. Correlation of morphology with biochemical and metabolic data. J Bone Joint Surg Am. 1971 Apr;53(3):523–537. [PubMed]
  • Mankin HJ, Johnson ME, Lippiello L. Biochemical and metabolic abnormalities in articular cartilage from osteoarthritic human hips. III. Distribution and metabolism of amino sugar-containing macromolecules. J Bone Joint Surg Am. 1981 Jan;63(1):131–139. [PubMed]
  • Schwartz ER, Leveille CR, Stevens JW, Oh WH. Proteoglycan structure and metabolism in normal and osteoarthritic cartilage of guinea pigs. Arthritis Rheum. 1981 Dec;24(12):1528–1539. [PubMed]
  • Sandy JD, Adams ME, Billingham ME, Plaas A, Muir H. In vivo and in vitro stimulation of chondrocyte biosynthetic activity in early experimental osteoarthritis. Arthritis Rheum. 1984 Apr;27(4):388–397. [PubMed]
  • Inerot S, Heinegård D, Audell L, Olsson SE. Articular-cartilage proteoglycans in aging and osteoarthritis. Biochem J. 1978 Jan 1;169(1):143–156. [PMC free article] [PubMed]
  • Santer V, White RJ, Roughley PJ. Proteoglycans from normal and degenerate cartilage of the adult human tibial plateau. Arthritis Rheum. 1981 May;24(5):691–700. [PubMed]
  • Cox MJ, McDevitt CA, Arnoczky SP, Warren RF. Changes in the chondroitin sulfate-rich region of articular cartilage proteoglycans in experimental osteoarthritis. Biochim Biophys Acta. 1985 Jun 18;840(2):228–234. [PubMed]
  • Carney SL, Billingham ME, Muir H, Sandy JD. Structure of newly synthesised (35S)-proteoglycans and (35S)-proteoglycan turnover products of cartilage explant cultures from dogs with experimental osteoarthritis. J Orthop Res. 1985;3(2):140–147. [PubMed]
  • Orford CR, Gardner DL, O'Connor P, Bates G, Swallow JJ, Brito-Babapulle LA. Ultrastructural alterations in glycosaminoglycans of dog femoral condylar cartilage after surgical division of an anterior cruciate ligament: a study with cupromeronic blue in a critical electrolyte concentration technique. J Anat. 1986 Oct;148:233–244. [PMC free article] [PubMed]
  • Teshima R, Treadwell BV, Trahan CA, Mankin HJ. Comparative rates of proteoglycan synthesis and size of proteoglycans in normal and osteoarthritic chondrocytes. Arthritis Rheum. 1983 Oct;26(10):1225–1230. [PubMed]
  • Mankin HJ, Lippiello L. Biochemical and metabolic abnormalities in articular cartilage from osteo-arthritic human hips. J Bone Joint Surg Am. 1970 Apr;52(3):424–434. [PubMed]
  • Telhag H, Lindberg L. A method for inducing osteoarthritic changes in rabbits' knees. Clin Orthop Relat Res. 1972 Jul-Aug;86:214–223. [PubMed]
  • Moskowitz RW, Davis W, Sammarco J, Martens M, Baker J, Mayor M, Burstein AH, Frankel VH. Experimentally induced degenerative joint lesions following partial meniscectomy in the rabbit. Arthritis Rheum. 1973 May-Jun;16(3):397–405. [PubMed]
  • McDevitt C, Gilbertson E, Muir H. An experimental model of osteoarthritis; early morphological and biochemical changes. J Bone Joint Surg Br. 1977 Feb;59(1):24–35. [PubMed]
  • Schwartz ER, Oh WH, Leveille CR. Experimentally induced osteoarthritis in guinea pigs: metabolic responses in articular cartilage to developing pathology. Arthritis Rheum. 1981 Nov;24(11):1345–1355. [PubMed]
  • Colombo C, Butler M, O'Byrne E, Hickman L, Swartzendruber D, Selwyn M, Steinetz B. A new model of osteoarthritis in rabbits. I. Development of knee joint pathology following lateral meniscectomy and section of the fibular collateral and sesamoid ligaments. Arthritis Rheum. 1983 Jul;26(7):875–886. [PubMed]
  • Vignon E, Arlot M, Hartmann D, Moyen B, Ville G. Hypertrophic repair of articular cartilage in experimental osteoarthrosis. Ann Rheum Dis. 1983 Feb;42(1):82–88. [PMC free article] [PubMed]
  • Bendele AM. Progressive chronic osteoarthritis in femorotibial joints of partial medial meniscectomized guinea pigs. Vet Pathol. 1987 Sep;24(5):444–448. [PubMed]
  • Bendele AM, Hulman JF. Spontaneous cartilage degeneration in guinea pigs. Arthritis Rheum. 1988 Apr;31(4):561–565. [PubMed]
  • Walton M. Degenerative joint disease in the mouse knee; histological observations. J Pathol. 1977 Oct;123(2):109–122. [PubMed]
  • Moskowitz RW, Goldberg VM. Osteophyte evolution: studies in an experimental partial meniscectomy model. J Rheumatol. 1987 May;14(Spec No):116–118. [PubMed]
  • Lukoschek M, Schaffler MB, Burr DB, Boyd RD, Radin EL. Synovial membrane and cartilage changes in experimental osteoarthrosis. J Orthop Res. 1988;6(4):475–492. [PubMed]
  • Pelletier JP, Martel-Pelletier J, Altman RD, Ghandur-Mnaymneh L, Howell DS, Woessner JF., Jr Collagenolytic activity and collagen matrix breakdown of the articular cartilage in the Pond-Nuki dog model of osteoarthritis. Arthritis Rheum. 1983 Jul;26(7):866–874. [PubMed]
  • Lindblad S, Hedfors E. Arthroscopic and immunohistologic characterization of knee joint synovitis in osteoarthritis. Arthritis Rheum. 1987 Oct;30(10):1081–1088. [PubMed]
  • Goldenberg DL, Egan MS, Cohen AS. Inflammatory synovitis in degenerative joint disease. J Rheumatol. 1982 Mar-Apr;9(2):204–209. [PubMed]
  • Cantatore FP, Benazzo F, Ribatti D, Lapadula G, D'Amico S, Tursi A, Pipitone V. Early alteration of synovial membrane in osteoarthrosis. Clin Rheumatol. 1988 Jun;7(2):214–219. [PubMed]
  • Altman RD, Fries JF, Bloch DA, Carstens J, Cooke TD, Genant H, Gofton P, Groth H, McShane DJ, Murphy WA, et al. Radiographic assessment of progression in osteoarthritis. Arthritis Rheum. 1987 Nov;30(11):1214–1225. [PubMed]
  • Schünke M, Tillmann B, Brück M, Müller-Ruchholtz W. Morphologic characteristics of developing osteoarthrotic lesions in the knee cartilage of STR/IN mice. Arthritis Rheum. 1988 Jul;31(7):898–905. [PubMed]
  • SOKOLOFF L. Natural history of degenerative joint disease in small laboratory animals. I. Pathological anatomy of degenerative joint disease in mice. AMA Arch Pathol. 1956 Aug;62(2):118–128. [PubMed]
  • JAY GE, Jr, SOKOLOFF L. Natural history of degenerative joint disease in small laboratory animals. II. Epiphyseal maturation and osteoarthritis of the knee of mice of inbred strains. AMA Arch Pathol. 1956 Aug;62(2):129–135. [PubMed]
  • Wilhelmi G, Faust R. Suitability of the C57 black mouse as an experimental animal for the study of skeletal changes due to ageing, with special reference to osteo-arthrosis and its response to tribenoside. Pharmacology. 1976;14(4):289–296. [PubMed]
  • Walton M. Degenerative joint disease in the mouse knee; radiological and morphological observations. J Pathol. 1977 Oct;123(2):97–107. [PubMed]
  • Walton M. Studies of degenerative joint disease in the mouse knee joint; scanning electron microscopy. J Pathol. 1977 Dec;123(4):211–217. [PubMed]
  • Walton M. Patella displacement and osteoarthrosis of the knee joint in mice. J Pathol. 1979 Apr;127(4):165–172. [PubMed]
  • Bingel SA, Sande RD, Wight TN. Undersulfated chondroitin sulfate in cartilage from a miniature poodle with spondyloepiphyseal dysplasia. Connect Tissue Res. 1986;15(4):283–302. [PubMed]
  • Pelletier JP, Martel-Pelletier J. Cartilage degradation by neutral proteoglycanases in experimental osteoarthritis. Suppression by steroids. Arthritis Rheum. 1985 Dec;28(12):1393–1401. [PubMed]
  • Arsever CL, Bole GG. Experimental osteoarthritis induced by selective myectomy and tendotomy. Arthritis Rheum. 1986 Feb;29(2):251–261. [PubMed]
  • Manicourt DH, Pita JC. Progressive depletion of hyaluronic acid in early experimental osteoarthritis in dogs. Arthritis Rheum. 1988 Apr;31(4):538–544. [PubMed]
  • Pidd JG, Gardner DL, Adams ME. Ultrastructural changes in the femoral condylar cartilage of mature American foxhounds following transection of the anterior cruciate ligament. J Rheumatol. 1988 Apr;15(4):663–669. [PubMed]
  • MURRAY DG. EXPERIMENTALLY INDUCED ARTHRITIS USING INTRA-ARTICULAR PAPAIN. Arthritis Rheum. 1964 Jun;7:211–219. [PubMed]
  • Bentley G. Papain-induced degenerative arthritis of the hip in rabbits. J Bone Joint Surg Br. 1971 May;53(2):324–337. [PubMed]
  • Scheck M, Sakovich L. Degenerative joint disease of the canine hip: experimental production by multiple papain and prednisone injections. Clin Orthop Relat Res. 1972 Jul-Aug;86:115–120. [PubMed]
  • Farkas T, Bihari-Varga M, Biró T. Thermoanalytical and histological study of intra-articular papain-induced degradation and repair of rabbit cartilage. I. Immature animals. Ann Rheum Dis. 1974 Jul;33(4):385–390. [PMC free article] [PubMed]
  • Farkas T, Bihari-Varga M, Biró T. Thermoanalytical and histological study of intra-articular papain-induced degradation and repair of rabbit cartilage. II. Mature animals. Ann Rheum Dis. 1976 Feb;35(1):23–26. [PMC free article] [PubMed]
  • Shaw NE, Lacey E. The influence of corticosteroids on normal and papain-treated articular cartilage in the rabbit. J Bone Joint Surg Br. 1973 Feb;55(1):197–205. [PubMed]
  • Havdrup T, Telhag H. Papain-induced changes in the knee joints of adult rabbits. Acta Orthop Scand. 1977;48(2):143–149. [PubMed]
  • Moriizumi T, Yamashita N, Okada Y. Papain-induced changes in the guinea pig knee joint with special reference to cartilage healing. Virchows Arch B Cell Pathol Incl Mol Pathol. 1986;51(6):461–474. [PubMed]
  • Kalbhen DA, Scherbach E, Felten K. Histological investigations of the antiarthrotic effect of tribenoside (Glyvenol) in experimental osteoarthrosis. J Rheumatol. 1983 Apr;10(2):267–281. [PubMed]
  • Williams JM, Brandt KD. Temporary immobilisation facilitates repair of chemically induced articular cartilage injury. J Anat. 1984 May;138(Pt 3):435–446. [PMC free article] [PubMed]
  • Williams JM, Brandt KD. Exercise increases osteophyte formation and diminishes fibrillation following chemically induced articular cartilage injury. J Anat. 1984 Dec;139(Pt 4):599–611. [PMC free article] [PubMed]
  • Williams JM, Brandt KD. Immobilization ameliorates chemically-induced articular cartilage damage. Arthritis Rheum. 1984 Feb;27(2):208–216. [PubMed]
  • Kruijsen MW, van den Berg WB, van de Putte LB, van den Broek WJ. Detection and quantification of experimental joint inflammation in mice by measurement of 99mTc-pertechnetate uptake. Agents Actions. 1981 Dec;11(6-7):640–642. [PubMed]
  • de Vries BJ, van den Berg WB, Vitters E, van de Putte LB. Quantitation of glycosaminoglycan metabolism in anatomically intact articular cartilage of the mouse patella: in vitro and in vivo studies with 35S-sulfate, 3H-glucosamine, and 3H-acetate. Rheumatol Int. 1986;6(6):273–281. [PubMed]
  • Kruijsen MW, van den Berg WB, van de Putte LB. Sequential alterations of periarticular structures in antigen-induced arthritis in mice. Histological observations on fibrous capsule, ligaments, bone and muscles, using whole joint sections. Br J Exp Pathol. 1983 Jun;64(3):298–305. [PMC free article] [PubMed]
  • Kruijsen MW, van den Berg WB, van de Putte LB. Influence of the severity and duration of murine antigen-induced arthritis on cartilage proteoglycan synthesis and chondrocyte death. Arthritis Rheum. 1985 Jul;28(7):813–819. [PubMed]
  • van den Berg WB, Kruijsen MW, van de Putte LB, van Beusekom HJ, van der Sluis-van der Pol M, Zwarts WA. Antigen-induced and zymosan-induced arthritis in mice: studies on in vivo cartilage proteoglycan synthesis and chondrocyte death. Br J Exp Pathol. 1981 Jun;62(3):308–316. [PMC free article] [PubMed]
  • Goldenberg DL, Egan MS, Cohen AS. Inflammatory synovitis in degenerative joint disease. J Rheumatol. 1982 Mar-Apr;9(2):204–209. [PubMed]
  • Katona G. Osteoarthritis--an inflammatory disease? Int J Tissue React. 1984;6(6):453–461. [PubMed]
  • Pelletier JP, Martel-Pelletier J, Ghandur-Mnaymneh L, Howell DS, Woessner JF., Jr Role of synovial membrane inflammation in cartilage matrix breakdown in the Pond-Nuki dog model of osteoarthritis. Arthritis Rheum. 1985 May;28(5):554–561. [PubMed]
  • Cooke TD. Immune pathology in polyarticular osteoarthritis. Clin Orthop Relat Res. 1986 Dec;(213):41–49. [PubMed]
  • Lindblad S, Hedfors E. Arthroscopic and immunohistologic characterization of knee joint synovitis in osteoarthritis. Arthritis Rheum. 1987 Oct;30(10):1081–1088. [PubMed]
  • Revell PA, Mayston V, Lalor P, Mapp P. The synovial membrane in osteoarthritis: a histological study including the characterisation of the cellular infiltrate present in inflammatory osteoarthritis using monoclonal antibodies. Ann Rheum Dis. 1988 Apr;47(4):300–307. [PMC free article] [PubMed]
  • Schalkwijk J, van den Berg WB, van de Putte LB, Joosten LA. Hydrogen peroxide suppresses the proteoglycan synthesis of intact articular cartilage. J Rheumatol. 1985 Apr;12(2):205–210. [PubMed]
  • Altman FP. A metabolic dysfunction in early murine osteoarthritis. Ann Rheum Dis. 1981 Jun;40(3):303–306. [PMC free article] [PubMed]
  • Coulais Y, Marcelon G, Cros J, Guiraud R. Etude d'un modèle expérimental d'arthrose. I.--Induction et étude ultrastructurale. Pathol Biol (Paris) 1983 Sep;31(7):577–582. [PubMed]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

Formats: