Application of tissue-engineered cartilage with BMP-7 gene to repair knee joint cartilage injury in rabbits
- 288 Downloads
Injured articular cartilage has a poor capacity for spontaneous healing. So far, satisfactory solution to this subsistent problem has not been found, but transgenic therapy may be a promising way. This study aims to evaluate the effectiveness of a tissue-engineered cartilage that was transfected with morphogenetic protein 7 (BMP 7) in repairing the cartilaginous defects of rabbit knee joints. Chondrocytes were transfected with BMP-7 gene (5 × 106 cells/ml), inoculated into the collagen-fibrin gel scaffolds, and cultured for 14 days. Then, the scaffolds were implanted onto the created defects (5.0 mm in diameter) in rabbits’ knee joints. After 12 weeks, the rabbits were sacrificed and histological sections were evaluated using modified O’Driscoll cartilage scores; In situ hybridization and immunohistochemistry were performed to detect the expression of BMP-7 mRNA and BMP-7 at the implanted site while the content of DNA and GAG was determined as well. A better quality of repairs was observed at the 12th week after implantation when compared to the control group using histological analyses. The content of DNA and specific secretion of GAG in the treatment group is statistically significant different compared with the control group. Gene therapy may be a promising treatment method, but the novel therapy approach needs further studies with respect to a longer follow-up period.
KeywordsBone morphogenetic protein-7 (BMP-7) Tissue-engineering cartilage Cartilage defect Gene
The authors are grateful for the support of Heilongjiang Postdoctoral Sustentation Fund, China (grant no. LRB05-299), National Postdoctoral Sustentation Fund, China (grant no. 20070410916).
Conflicts of interest
The authors have no conflicts of interest to declare in relation to this article.
- 1.Bartlett W, Skinner JA, Gooding CR, Carrington RW, Flanagan AM, Briggs TW, Bentley G (2005) Autologous chondrocyte implantation versus matrix-induced autologous chondrocyte implantation for osteochondral defects of the knee: a prospective, randomised study. J Bone Joint Surg Br 87:640–645CrossRefPubMedGoogle Scholar
- 7.Flechtenmacher J, Huch K, Thonar EJ, Mollenhauer JA, Davies SR, Schmid TM, Puhl W, Sampath TK, Aydelotte MB, Kuettner KE (1996) Recombinant human osteogenic protein 1 is a potent stimulator of the synthesis of cartilage proteoglycans and collagens by human articular chondrocytes. Arthritis Rheum 39:1896–1904CrossRefPubMedGoogle Scholar
- 10.Horas U, Pelinkovic D, Herr G, Aigner T, Schnettler R (2003) Autologous chondrocyte implantation and osteochondral cylinder transplantation in cartilage repair of the knee joint. A prospective, comparative trial. J Bone Joint Surg Am 85A:185–192Google Scholar
- 11.Huch K, Wilbrink B, Flechtenmacher J, Koepp HE, Aydelotte MB, Sampath TK, Kuettner KE, Mollenhauer J, Thonar EJ (1997) Effects of recombinant human osteogenic protein 1 on the production of proteoglycan, prostaglandin E2, and interleukin-1 receptor antagonist by human articular chondrocytes cultured in the presence of interleukin-1beta. Arthritis Rheum 40:2157–2161CrossRefPubMedGoogle Scholar
- 14.Koga H, Engebretsen L, Brinchmann JE, Muneta T, Sekiya I (2009) Mesenchymal stem cell-based therapy for cartilage repair: a review. Knee Surg Sports Traumatol Arthrosc. doi: 10.1007/s00167-009-0782-4
- 18.Loken S, Ludvigsen TC, Hoysveen T, Holm I, Engebretsen L, Reinholt FP (2009) Autologous chondrocyte implantation to repair knee cartilage injury: ultrastructural evaluation at 2 years and long-term follow-up including muscle strength measurements. Knee Surg Sports Traumatol Arthrosc 16:398–404Google Scholar
- 20.Marcacci M, Berruto M, Brocchetta D, Delcogliano A, Ghinelli D, Gobbi A, Kon E, Pederzini L, Rosa D, Sacchetti GL, Stefani G, Zanasi S (2005) Articular cartilage engineering with Hyalograft C: 3-year clinical results. Clin Orthop Relat Res 96–105Google Scholar
- 26.Wakitani S, Nawata M, Tensho K, Okabe T, Machida H, Ohgushi H (2007) Repair of articular cartilage defects in the patello-femoral joint with autologous bone marrow mesenchymal cell transplantation: three case reports involving nine defects in five knees. J Tissue Eng Regen Med 1:74–79CrossRefPubMedGoogle Scholar