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An experimental study of COMP (cartilage oligomeric matrix protein) in the rabbit menisci

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Abstract

Introduction

Secondary knee osteoarthritis (OA) is currently associated with meniscal injuries, but the pathogenesis is unclear. We analyzed the distribution of cells and cartilage oligomeric matrix protein (COMP) and its changes in the early stages of degeneration in meniscus.

Method

Ten New Zealand rabbits underwent anterior cruciate ligament (ACL)-transection of the right knee-joint. Left knee-joints were used as controls. The animals were killed at 4 and 12 weeks. Gross injuries in meniscus and articular cartilage were scored. Meniscal tissues were immunostained with a specific antibody against COMP, with Ki-67, using TUNEL-assay and alcian blue stain. The number of cells was counted.

Results

At 4 weeks post-ACL-transection, 2/5 of the operated knees showed articular damages and medial menisci tears. Menisci showed a weak increase of cells, higher in cells under division and an increase of apoptosis, COMP and proteoglycans.

At 12 weeks, 5/5 of the medial menisci and 2/5 of lateral menisci presented tears, and osteoarthritic changes were seen in the cartilage of all the operated knees. Meniscal cells reverted to normal number, while active cell division decreased below normal, apoptotic events were still high, COMP remained elevated, and glycosaminoglycans were even more elevated.

Conclusion

Extracellular matrix changes and altered cell distribution occur early in the degenerative meniscus. There is a close relationship between changes in the articular cartilage and the menisci at the onset of secondary OA.

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References

  1. Kuettner KE, Goldbeg VM (1995) Introduction. In: Kuettner KE, Goldbeg VM (eds) Osteoarthritic disorders. American Academy of Orthopedic Surgeons, Rosemont, pp xxi–xxv

    Google Scholar 

  2. Hauser N, Paulsson M, Kale AA, Di Cesare PE (1995) Tendon extracellular matrix contains pentameric thrombospondin-4 (TSP-4). FEBS Lett 368:307–310

    Article  PubMed  CAS  Google Scholar 

  3. Rosenberg K, Olsson H, Mörgelin M, Heinegård D (1998) Cartilage oligomeric matrix protein shows high affinity zinc-dependent interaction with triple helical collagen. J Biol Chem 273:20397–20403

    Article  PubMed  CAS  Google Scholar 

  4. Di Cesare PE, Fang C, Leslie MP et al (1999) Localization and expression of cartilage oligomeric matrix protein by human rheumatoid and osteoarthritic synovium and cartilage. J Orthop Res 17:437–445

    Article  PubMed  CAS  Google Scholar 

  5. Holden P, Meadows RS, Chapman KL, Grant ME, Kadler KE, Briggs MD (2001) Cartilage oligomeric matrix protein interacts with type IX collagen, and disruptions to these interactions identify a pathogenetic mechanism in a bone dysplasia family. J Biol Chem 276:6046–6055

    Article  PubMed  CAS  Google Scholar 

  6. Hedbom E, Antonsson P, Hjerpe A et al (1992) Cartilage matrix proteins. An acidic oligomeric protein (COMP) detected only in cartilage. J Biol Chem 267:6132–6136

    PubMed  CAS  Google Scholar 

  7. DiCesare PE, Mörgelin M, Mann K, Paulsson M (1994) Cartilage oligomeric matrix protein and thrombospondin 1. Purification from articular cartilage, electron microscopic structure, and chondrocyte binding. Eur J Biochem 223:927–937

    Article  PubMed  CAS  Google Scholar 

  8. Thur J, Rosenberg K, Nitsche DP et al (2001) Mutations in cartilage oligomeric matrix protein causing pseudoachondroplasis and multiple epiphyseal displasia affect binding of calcium and collagen I, II, and IX. J Biol Chem 276:6083–6092

    Article  PubMed  CAS  Google Scholar 

  9. Guo Y, Bozic D, Malashkevich VN, Kammerer RA, Schulthess T, Engel J (1998) All-transretinol, vitamin D and other hydrophobic compounds bind to the axial pore of the five-stranded coiled-coil domain of cartilage oligomeric matrix protein. EMBO J 17:5265–5272

    Article  PubMed  CAS  Google Scholar 

  10. Chen H, Deere M, Hecht JT, Lawler J (2000) Cartilage oligomeric matrix protein is a calcium-binding protein, and a mutation in its type 3 repeats causes conformational changes. J Biol Chem 275:26538–26544

    Article  PubMed  CAS  Google Scholar 

  11. Forslind K, Eberhardt K, Jonsson A, Saxne T (1992) Increased serum concentrations of cartilage oligomeric matrix protein. A prognostic marker in early rheumatoid arthritis. Br J Rheumatol 31:593–598

    Article  PubMed  CAS  Google Scholar 

  12. Sharif M, Saxne T, Shepstone L et al (1995) Relationship between serum cartilage oligomeric matrix protein levels and disease progression in osteoarthritis of the knee joint. Br J Rheumatol 34:306–310

    Article  PubMed  CAS  Google Scholar 

  13. Neidhart M, Hauser N, Paulsson M, Di Cesare PE, Michel BA, Häuselmann HJ (1997) Small fragments of cartilage oligomeric matrix protein in synovial fluid and serum as markers for cartilage degradation. Br J Rheumatol 36:1151–1160

    Article  PubMed  CAS  Google Scholar 

  14. Petersson IF, Boegård T, Dahlström J, Svennson B, Heinegård D, Saxne T (1998) Bone scan and serum markers of bone and cartilage in patients with knee pain and osteoarthritis. Osteoarthritis Cartilage 6:33–39

    Article  PubMed  CAS  Google Scholar 

  15. Petersson IF, Boegård TB, Svensson D, Heinegård D, Saxne T (1998) Changes in cartilage and bone metabolism identified by serum markers in early osteoarthritis of the knee joint. Br J Rheumatol 37:46–50

    Article  PubMed  CAS  Google Scholar 

  16. Otterness IG, Swindell AC, Zimmerer RO, Poole AR, Ionescu M, Weiner E (2000) An analysis of 14 molecular markers for monitoring osteoarthritis: segregation of the markers into clusters and distinguishing osteoarthritis at baseline. Osteoarthritis Cartilage 8:180–185

    Article  PubMed  CAS  Google Scholar 

  17. Vilím V, Olejárová M, Macháček S, Gatterová J, Kraus VB, Pavelka K (2002) Serum levels of cartilage oligomeric matrix protein (COMP) correlate with radiographic progression of knee osteoarthritis. Osteoarthritis Cartilage 10:707–713

    Article  PubMed  Google Scholar 

  18. Wisłowska M, Jabłońska B (2005) Cartilage oligomeric matrix protein in serum in systemic lupus erythematosus and knee osteoarthritis. Preliminary communication. Rheumatol Int 25:373–378

    Article  PubMed  Google Scholar 

  19. Gómez-Barrena E, Lindroos L, Čeponis A et al (2006) Cartilage oligomeric matrix protein (COMP) is modified by intra-articular liposomal clodronate in an experimental model of arthritis. Clin Exp Rheumatol 24(6):622–628

    PubMed  Google Scholar 

  20. Rimoin DL, Rasmussen IM, Briggs MD et al (1994) A large family with features of pseudoachondroplasia and multiple epiphyseal dysplasia: exclusion of seven candidate gene loci that encode proteins of the cartilage extracellular matrix. Hum Genet 93:236–242

    Article  PubMed  CAS  Google Scholar 

  21. Stevens JW (1999) Pseudoachondroplastic dysplasia: an Iowa review from human to mouse. Iowa Orthop J 19:53–65

    PubMed  CAS  Google Scholar 

  22. Kennedy J, Jackson G, Ramsden S et al (2005) COMP mutation screening as an aid for the clinical diagnosis and counselling of patients with a suspected diagnosis of pseudoachondroplasia or multiple epiphyseal dysplasia. Eur J Hum Genet 13:547–555

    Article  PubMed  CAS  Google Scholar 

  23. Yoshioka M, Coutts RD, Amiel D, Hacker SA (1996) Characterization of a model of osteoarthritis in the rabbit knee. Osteoarthritis Cartilage 4(2):87–98

    Article  PubMed  CAS  Google Scholar 

  24. Meachim G (1972) Light microscopy of Indian ink preparations of fibrillated cartilage. Ann Rheum Dis 31(6):457–464

    Article  PubMed  CAS  Google Scholar 

  25. Adams ME, Billingham ME, Muir H (1983) The glycosaminoglycans in menisci in experimental and natural osteoarthritis. Arthritis Rheum 26:69–76

    Article  PubMed  CAS  Google Scholar 

  26. Herrero-Beaumont G, Guerrero R, Sánchez-Pernaute O et al (2001) Cartilage and bone biological markers in the synovial fluid of osteoarthritic patients after hyaluronan injections in the knee. Clin Chim Acta 308:107–115

    Article  PubMed  CAS  Google Scholar 

  27. Moon MS, Kim JM, Ok IY (1984) The normal and regenerated meniscus in rabbits. Morphologic and histologic studies. Clin Orthop Relat Res 182:264–269

    PubMed  Google Scholar 

  28. Hellio Le Graverand MP, Vignon E, Otterness IG, Hart DA (2001) Early changes in lapine menisci during osteoarthritis development (Part I): cellular and matrix alterations. Osteoarthritis Cartilage 9:56–64

    Article  PubMed  CAS  Google Scholar 

  29. Hellio Le Graverand MP, Vignon E, Otterness IG, Hart DA (2001) Early changes in lapine menisci during osteoarthritis development (Part II): molecular alterations. Osteoarthritis Cartilage 9:65–72

    Article  PubMed  CAS  Google Scholar 

  30. Ochi M, Kanda T, Sumen Y, Ikuta Y (1997) Changes in the permeability and histologic findings of rabbit menisci after immobilization. Clin Orthop Relat Res 334:305–315

    Article  PubMed  Google Scholar 

  31. Nishida M, Higuchi H, Kobayashi Y, Takagishi K (2005) Histological and biochemical changes of experimental meniscus tear in the dog knee. J Orthop Sci 10:406–413

    Article  PubMed  CAS  Google Scholar 

  32. Hellio Le Graverand MP, Sciore P, Eggerer J, Rattner JP, Vignon E, Barclay L et al (2001) Formation and phenotype of cell clusters in osteoarthritic meniscus. Arthritis Rheum 44(8):1808–1818

    Article  PubMed  CAS  Google Scholar 

  33. Hashimoto S, Takahashi K, Ochs RL, Coutts RD, Amiel D, Lotz M (1999) Nitric oxide production and apoptosis in cells of the meniscus during experimental osteoarthritis. Arthritis Rheum 42:2123–2131

    Article  PubMed  CAS  Google Scholar 

  34. Herwig J, Egner E, Buddecke E (1984) Chemical changes of human knee joint menisci in various stages of degeneration. Ann Rheum Dis 43:635–640

    Article  PubMed  CAS  Google Scholar 

  35. Buckwalter JA, Mankin HJ (1997) Instructional course lecture. The American academy of orthopaedic surgeons—articular cartilage. Part II: degeneration and osteoarthrosis, repair, regeneration and transplantation. J Bone Joint Surg A 79:612–632

    Google Scholar 

  36. Nguyen BQ, Fife RS (1986) Vitreous contains a cartilage related protein. Exp Eye Res 43:375–382

    Article  PubMed  CAS  Google Scholar 

  37. Riessen R, Fenchel M, Chen H, Axel DI, Karsch KR, Lawler J (2001) Cartilage oligomeric matrix protein (thrombospondin-5) is expressed by human vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 21:47–54

    Article  PubMed  CAS  Google Scholar 

  38. Xiao Y, Kleeff J, Guo J et al (2004) Cartilage oligomeric matrix protein expression in hepatocellular carcinoma and the cirrhotic liver. J Gastroenterol Hepatol 19:296–302

    Article  PubMed  CAS  Google Scholar 

  39. Gagarina V, Carlberg AL, Pereira-Mouries L, Hall DJ (2008) Cartilage oligomeric matrix protein protects cells against death by elevating members of the IAP family of survival proteins. J Biol Chem 283:648–659

    Article  PubMed  CAS  Google Scholar 

  40. Hashimoto Y, Tomiyama T, Yamano Y, Mori H (2003) Mutation (D472Y) in the type 3 repeat domain of cartilage oligomeric matrix protein affects its early vesicle trafficking in endoplasmic reticulum and induces apoptosis. Am J Pathol 163:101–110

    Article  PubMed  CAS  Google Scholar 

  41. Oldberg A, Antonsson P, Lindblom K, Heinegård D (1992) COMP (cartilage oligomeric matrix protein) is structurally related to the thrombospondins. J Biol Chem 267:22346–22350

    PubMed  CAS  Google Scholar 

  42. Di Cesare PE, Carlson CS, Stollerman ES, Chen FS, Leslie M, Perris R (1997) Expression of cartilage oligomeric matrix protein by human synovium. FEBS Lett 412:249–252

    Article  PubMed  CAS  Google Scholar 

  43. Fang C, Johnson D, Leslie MP, Carlson CS, Robbins M, Di Cesare PE (2001) Tissue distribution and measurement of cartilage oligomeric matrix protein in patients with magnetic resonance imaging detected bone bruises after acute anterior cruciate ligament tears. J Orthop Res 19:634–641

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Dr. Carmen Gómez-Guerrero and Guadalupe Ortiz-Muñoz for the excellent technical assistance in histological aspects of the study. The research complied with national legislation and with the National Institute of Health Guide for the Care and Use of Laboratory Animals.

Conflict of interest

The authors did not receive payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity.

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Correspondence to Mariano López-Franco.

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López-Franco, M., López-Franco, O., Murciano-Antón, M.A. et al. An experimental study of COMP (cartilage oligomeric matrix protein) in the rabbit menisci. Arch Orthop Trauma Surg 131, 1167–1176 (2011). https://doi.org/10.1007/s00402-011-1332-3

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  • DOI: https://doi.org/10.1007/s00402-011-1332-3

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