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Type II collagen synthesis in the articular cartilage of a rabbit model of osteoarthritis: expression of type II collagen C-propeptide and mRNA especially during early-stage osteoarthritis

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Journal of Orthopaedic Science

Abstract

Background

The aim of this study was to observe time course changes in type II collagen synthesis in various regions of articular cartilage affected with osteoarthritis (OA) by examining the expression of type II collagen C-propeptide (pCOL II-C) and mRNA in a rabbit OA model.

Methods

Osteoarthritis was experimentally induced by partial lateral meniscectomy in the knees of Japanese white rabbits. The cartilage of the animals was then examined histologically over time. The degenerative area of articular cartilage was divided into three areas, according to the degree of degeneration. The ability to synthesize type II collagen was estimated by the immunohistological staining of pCOL II-C and the in situ hybridization of mRNA in type II collagen.

Results

The positive rate of pCOL II-C immunostaining in chondrocytes was highest in the central-degenerative region 1 week after surgery, and the highest rate in the para-degenerative region was observed 2 and 4 weeks after surgery. The percentage of pCOL II-C positive cells increased as the histological degeneration score increased to moderate degeneration and then decreased with further progression of the severity of cartilage degeneration. Examination by in situ hybridization revealed that the regions marked by strong pCOL II-C mRNA expression were similar to those indicated by the immunohistology results.

Conclusions

These results suggest that the type II collagen-synthesizing potential of chondrocytes is highest in moderately degenerated areas of OA articular cartilage. Cartilage repair continues to be seen even as OA advances, although the reaction varies depending on the stage of OA.

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References

  1. H Nakajima T Goto O Horikawa T Kikuchi M Shinmei (1998) ArticleTitleLocalization of carboxy-terminal type II procollagen peptide (pCOL-II-C) and type II collagen in the repair tissue of full-thickness articular cartilage defect Connect Tissue Res 37 195–204 10.3109/03008209809002439 Occurrence Handle10.3109/03008209809002439 Occurrence Handle1:CAS:528:DyaK1cXnt1Oiu7g%3D Occurrence Handle9862221

    Article  CAS  PubMed  Google Scholar 

  2. F Nelson L Dahlberg S Laverty A Reiner I Pidoux M Ionescu et al. (1998) ArticleTitleEvidence for altered synthesis of type II collagen in patients with osteoarthritis J Clin Invest 102 2115–25 10.1172/JCI4853 Occurrence Handle10.1172/JCI4853 Occurrence Handle1:CAS:528:DyaK1MXmtFKq Occurrence Handle9854047

    Article  CAS  PubMed  Google Scholar 

  3. AR Poole F Nelson A Hollander A Reiner I Pidoux M Ionescu (1995) ArticleTitleCollagen II turnover in joint diseases Acta Orthop Scand 66 IssueIDSuppl 266 88–91

    Google Scholar 

  4. M Shinmei Y Inamori Y Yoshihara T Kikuchi T Hayakawa (1992) The potential of cartilage markers in joint fluid for drug evaluation KE Kuettner R Schleyerbach JG Peyron VC Hascall (Eds) Articular cartilage and osteoarthritis Raven New York 597–609

    Google Scholar 

  5. M Shinmei K Ito S Matsuyama Y Yoshihara K Matsuzawa (1993) ArticleTitleJoint fluid carboxy-terminal type II procollagen peptide as a marker of cartilage collagen biosynthesis Osteoarthritis Cartilage 1 121–8 10.1016/S1063-4584(05)80027-5 Occurrence Handle10.1016/S1063-4584(05)80027-5 Occurrence Handle1:STN:280:DyaK2s%2FktVOqtA%3D%3D Occurrence Handle8886088

    Article  CAS  PubMed  Google Scholar 

  6. C Colombo M Butler E O'Byrne L Hickman D Swartzendruber M Selwyn et al. (1983) ArticleTitleA new model of osteoarthritis in rabbits. I. Development of knee joint pathology following lateral meniscectomy and section of the fubular collateral and sesamoid ligaments Arthritis Rheum 26 875–86 10.1002/art.1780260709 Occurrence Handle10.1002/art.1780260709 Occurrence Handle1:STN:280:DyaL3s3ls1OgsQ%3D%3D Occurrence Handle6688183

    Article  CAS  PubMed  Google Scholar 

  7. HU Choi LH Tang TL Johnson S Pal LC Rosenberg A Reiner et al. (1983) ArticleTitleIsolation and characterization of a 35,000 molecular weight subunit fetal cartilage matrix protein J Biol Chem 258 655–61 Occurrence Handle1:CAS:528:DyaL3sXmslCgug%3D%3D Occurrence Handle6401297

    CAS  PubMed  Google Scholar 

  8. Y Okada M Shinmei O Tanaka K Naka A Kimura I Nakanishi et al. (1992) ArticleTitleLocalization of matrix metalloproteinase 3 (stromelysin) in osteoarthritic cartilage and synovium Lab Invest 66 680–90 Occurrence Handle1:STN:280:DyaK383pt1Ggsg%3D%3D Occurrence Handle1602738

    CAS  PubMed  Google Scholar 

  9. H Takaishi H Yamada Y Yabe (1997) ArticleTitlePreferential expression of alternatively spliced transcript of type II procollagen in the rabbit notochordal remnant and developing fibrocartilages Biochim Biophys Acta 1350 253–8 Occurrence Handle1:CAS:528:DyaK2sXpt1ymsA%3D%3D Occurrence Handle9061018

    CAS  PubMed  Google Scholar 

  10. H Takaishi O Nemoto M Shiota T Kikuchi H Yamada M Yamagishi et al. (1997) ArticleTitleType-II collagen gene expression is transiently upregulated in experimentally induced degeneration of rabbit intervertebral disc J Orthop Res 15 528–38 10.1002/jor.1100150408 Occurrence Handle10.1002/jor.1100150408 Occurrence Handle1:CAS:528:DyaK2sXntVClu7g%3D Occurrence Handle9379262

    Article  CAS  PubMed  Google Scholar 

  11. H Nakajima M Shinmei K Ito S Matsuyama T Kikuchi H Honda (1997) ArticleTitleLocalization of carboxy-terminal type II procollagen peptide (pCOL-II-C) in diseased cartilage J Orthop Sci 2 229–38 10.1007/BF02489043 Occurrence Handle10.1007/BF02489043

    Article  Google Scholar 

  12. LS Lohmander Y Yoshihara H Roos T Kobayashi H Yamada M Shinmei (1996) ArticleTitleProcollagen II C-propeptide in joint fluid: changes in concentrations with age, time after knee injury and osteoarthritis J Rheumatol 23 1765–9 Occurrence Handle1:CAS:528:DyaK28XmsFyhtL0%3D Occurrence Handle8895155

    CAS  PubMed  Google Scholar 

  13. H Kobayashi T Saito T Koshino (2002) ArticleTitleImmunolocalization of carboxy-terminal type II procollagen peptide in regenerated articular cartilage of osteoarthritic knees after reduction of mechanical stress Osteoarthritis Cartilage 10 870–8 10.1053/joca.2002.0839 Occurrence Handle10.1053/joca.2002.0839 Occurrence Handle1:STN:280:DC%2BD38nnsFKmuw%3D%3D Occurrence Handle12435332

    Article  CAS  PubMed  Google Scholar 

  14. T Aigner SI Vornehm G Zeiler J Dudhia K von der Mark MT Bayliss (1997) ArticleTitleSuppression of cartilage matrix gene expression in upper zone chondrocytes of osteoarthritic cartilage Arthritis Rheum 40 562–9 10.1002/art.1780400323 Occurrence Handle10.1002/art.1780400323 Occurrence Handle1:CAS:528:DyaK2sXit1yjsbg%3D Occurrence Handle9082945

    Article  CAS  PubMed  Google Scholar 

  15. T Aigner H Stoss G Weseloh G Zeiler K von der Mark (1992) ArticleTitleActivation of collagen type II expression in osteoarthritic and rheumatoid cartilage Virchows Arch B Cell Pathol Mol Pathol 62 337–45 10.1007/BF02899701 Occurrence Handle10.1007/BF02899701 Occurrence Handle1:STN:280:DyaK3s%2FovVKisA%3D%3D

    Article  CAS  Google Scholar 

  16. T Aigner W Bertling H Stoss G Weseloh K von der Mark (1993) ArticleTitleIndependent expression of fibril-forming collagens I, II, and III in chondrocytes of human osteoarthritic cartilage J Clin Invest 91 829–37 10.1172/JCI116303 Occurrence Handle10.1172/JCI116303 Occurrence Handle1:CAS:528:DyaK3sXitFSks70%3D Occurrence Handle7680669

    Article  CAS  PubMed  Google Scholar 

  17. T Aigner U Dietz H Stoss K von der Mark (1995) ArticleTitleDifferential expression of collagen types I, II, and X in human osteophytes Lab Invest 73 236–43 Occurrence Handle1:CAS:528:DyaK28Xit12lsLo%3D Occurrence Handle7637324

    CAS  PubMed  Google Scholar 

  18. JR Matyas LJ Sandell ME Adams (1997) ArticleTitleGene expression of type II collagens in chondro-osteophytes in experimental osteoarthritis Osteoarthritis Cartilage 5 99–105 10.1016/S1063-4584(97)80003-9 Occurrence Handle10.1016/S1063-4584(97)80003-9 Occurrence Handle1:STN:280:DyaK2s3otFGisQ%3D%3D Occurrence Handle9135821

    Article  CAS  PubMed  Google Scholar 

  19. D Pfander R Rahmanzadeh EE Scheller (1999) ArticleTitlePresence and distribution of collagen II, collagen I, fibronectin, and tenascin in rabbit normal and osteoarthritic cartilage J Rheumatol 26 386–94 Occurrence Handle1:CAS:528:DyaK1MXht1yjt7c%3D Occurrence Handle9972974

    CAS  PubMed  Google Scholar 

  20. R Stoop PM van der Kraan P Buma AD Hollander AR Poole WB van den Berg (1999) ArticleTitleDenaturation of type II collagen in articular cartilage in experimental murine arthritis: evidence for collagen degradation in both reversible and irreversible cartilage damage J Pathol 188 329–37 10.1002/(SICI)1096-9896(199907)188:3<329::AID-PATH371>3.0.CO;2-B Occurrence Handle10.1002/(SICI)1096-9896(199907)188:3<329::AID-PATH371>3.0.CO;2-B Occurrence Handle1:CAS:528:DyaK1MXltVKrurk%3D Occurrence Handle10419604

    Article  CAS  PubMed  Google Scholar 

  21. R Stoop PM van der Kraan P Buma AP Hollander RC Billinghurst AR Poole et al. (1999) ArticleTitleType II collagen degradation in spontaneous osteoarthritis in C57B1/6 and BALB/c mice Arthritis Rheum 42 2381–9 10.1002/1529-0131(199911)42:11<2381::AID-ANR17>3.0.CO;2-E Occurrence Handle10.1002/1529-0131(199911)42:11<2381::AID-ANR17>3.0.CO;2-E Occurrence Handle1:CAS:528:DyaK1MXnvVShsLY%3D Occurrence Handle10555034

    Article  CAS  PubMed  Google Scholar 

  22. R Stoop P Buma PM van der Kraan AP Hollander RC Billinghurst THM Meijers et al. (2001) ArticleTitleType II collagen degradation in articular cartilage fibrillation after anterior cruciate ligament transection in rats Osteoarthritis Cartilage 9 308–15 10.1053/joca.2000.0390 Occurrence Handle10.1053/joca.2000.0390 Occurrence Handle1:STN:280:DC%2BD3MzjtVGjsQ%3D%3D Occurrence Handle11399094

    Article  CAS  PubMed  Google Scholar 

  23. K Nakata S Miyamoto S Bernier M Tanaka A Utani P Krebsbach et al. (1996) ArticleTitleThe C-propeptide of type II procollagen binds to the enhancer region of the type II procollagen gene and regulates its transcription Ann NY Acad Sci 785 307–8 Occurrence Handle1:CAS:528:DyaK28XkvVahtbs%3D Occurrence Handle8702163 Occurrence Handle10.1111/j.1749-6632.1996.tb56292.x

    Article  CAS  PubMed  Google Scholar 

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Hotta, H., Yamada, H., Takaishi, H. et al. Type II collagen synthesis in the articular cartilage of a rabbit model of osteoarthritis: expression of type II collagen C-propeptide and mRNA especially during early-stage osteoarthritis. J Orthop Sci 10, 595–607 (2005). https://doi.org/10.1007/s00776-005-0947-z

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  • DOI: https://doi.org/10.1007/s00776-005-0947-z

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