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Journal of orthopaedic research : official publication of the Orthopaedic Research Society2003; 21(4); 573-583; doi: 10.1016/S0736-0266(02)00264-4

Acceleration of cartilage repair by genetically modified chondrocytes over expressing bone morphogenetic protein-7.

Abstract: Cartilage has a limited capacity to heal. Although chondrocyte transplantation is a useful therapeutic strategy, the repair process can be lengthy. Previously we have shown that over expression of bone morphogenetic protein-7 (BMP-7) in chondrocytes by adenovirus-mediated gene transfer leads to increased matrix synthesis and cartilage-like tissue formation in vitro. In this context we hypothesized that implantation of genetically modified chondrocytes expressing BMP-7 would accelerate the formation of hyaline-like repair tissue in an equine model of cartilage defect repair. Methods: Chondrocytes treated with adenovirus vector encoding BMP-7 (AdBMP-7) or as control, an adenovirus vector encoding an irrelevant gene (Escherichia coli cytosine deaminase, AdCD) were implanted into extensive (15 mm diameter) articular cartilage defects in the patellofemoral joints of 10 horses. Biopsies were performed to evaluate early healing at 4 weeks. At the terminal time point of 8 months, repairs were assessed for morphology, MRI appearance, compressive strength, biochemical composition and persistence of implanted cells. Results: Four weeks after surgery AdBMP-7-treated repairs showed an increased level of BMP-7 expression and accelerated healing, with markedly more hyaline-like morphology than control. Quantitative real-time polymerase chain reaction (PCR) analysis of the repair tissue 8 months after surgery showed that few implanted cells persisted. By this time, the controls had healed similarly to the AdBMP-7-treated defects, and no difference was detected in the morphologic, biochemical or biomechanical properties of the repair tissues from the two treatment groups. Conclusions: Implantation of genetically modified chondrocytes expressing BMP-7 accelerates the appearance of hyaline-like repair tissue in experimental cartilage defects. Conclusions: Rehabilitation after cell-based cartilage repair can be prolonged, leading to decreased patient productivity and quality of life. This study shows the feasibility of using genetically modified chondrocytes to accelerate cartilage healing.
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Publication Date: 2003-06-12 PubMed ID: 12798054DOI: 10.1016/S0736-0266(02)00264-4Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't
  • Research Support
  • U.S. Gov't
  • P.H.S.

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article focuses on accelerating the healing process of cartilage by using genetically modified chondrocytes, which have been treated to over express the protein BMP-7.

Research context and hypothesis

  • The context for this research arises from the limited capacity of cartilage to heal and the significant time commitment involved in carilage repair through chondrocyte transplantation.
  • Researchers developed a hypothesis around the ability of an over expressed protein, bone morphogenetic protein-7 (BMP-7), to accelerate the formation of hyaline-like repair tissue.
  • The hypothesis was tested using an equine model of cartilage defect repair.

Methods of the study

  • Chondrocytes were treated with either an adenovirus vector encoding BMP-7 or a control vector encoding an irrelevant gene, then implanted into significant cartilage defects in the patellofemoral joints of 10 horses.
  • Early healing was measured through biopsies at 4 weeks post-surgery.
  • New tissues were evaluated through morphology, MRI appearance, compressive strength, biochemical composition and persistence of implanted cells.
  • The controls were compared with the AdBMP-7-treated defects after 8 months.

Results of the study

  • Repairs treated with BMP-7 showed increased expression of BMP-7 and accelerated healing, particularly a higher hyaline-like morphology than the control group.
  • Real-time polymerase chain reaction (PCR) analysis of the tissue after 8 months revealed that few implanted cells survived.
  • By the end of 8 months, controls healed comparably to the BMP-7-treated groups, with no difference detected in morphologic, biochemical or biomechanical properties of the repair tissues.

Conclusions drawn from the study

  • The results show that the use of genetically modified chondrocytes expressing BMP-7 can accelerate the formation of hyaline-like repair tissue in cartilage defects.
  • This acceleration of the healing process could potentially shorten the rehabilitation period after cell-based cartilage repair, therefore enhancing productivity and quality of life of patients.
  • However, there remains a need for further research to understand the longevity and durability of these results, as differences between the treated and control groups disappeared after 8 months.

Cite This Article

APA
Hidaka C, Goodrich LR, Chen CT, Warren RF, Crystal RG, Nixon AJ. (2003). Acceleration of cartilage repair by genetically modified chondrocytes over expressing bone morphogenetic protein-7. J Orthop Res, 21(4), 573-583. https://doi.org/10.1016/S0736-0266(02)00264-4

Publication

Journal of orthopaedic research : official publication of the Orthopaedic Research Society
ISSN: 0736-0266
NlmUniqueID: 8404726
Country: United States
Language: English
Volume: 21
Issue: 4
Pages: 573-583

Researcher Affiliations

Hidaka, Chisa
  • Laboratory for Soft Tissue Research, Hospital for Special Surgery, New York, NY 10021, USA.
Goodrich, Laurie R
    Chen, Chih-Tung
      Warren, Russell F
        Crystal, Ronald G
          Nixon, Alan J

            MeSH Terms

            • Adenoviridae / genetics
            • Animals
            • Bone Morphogenetic Protein 7
            • Bone Morphogenetic Proteins / genetics
            • Cartilage / injuries
            • Cartilage / pathology
            • Cartilage Diseases / pathology
            • Cartilage Diseases / therapy
            • Cartilage Diseases / veterinary
            • Chondrocytes / physiology
            • Chondrocytes / transplantation
            • Compressive Strength
            • DNA / analysis
            • Female
            • Gene Expression
            • Genetic Therapy / methods
            • Genetic Vectors
            • Graft Survival
            • Horse Diseases / pathology
            • Horse Diseases / therapy
            • Horses
            • Knee Joint / diagnostic imaging
            • Knee Joint / pathology
            • Male
            • Radiography
            • Synovial Fluid
            • Transforming Growth Factor beta
            • Wound Healing

            Grant Funding

            • RR07059-05 / NCRR NIH HHS
            • T32AR07281 / NIAMS NIH HHS

            Citations

            This article has been cited 45 times.
            1. Gao X, Wright N, Huard M, Tan J, Ruzbarsky J, Lu A, Chubb L, Tuan R, Philippon MJ, Wang Y, Huard J. Comparison of 5 BMPs for their chondrogenic potentials and microfracture-mediated cartilage repair using heparin/PEAD coacervate sustained release polymer. Bioact Mater 2025 Oct;52:588-603.
              doi: 10.1016/j.bioactmat.2025.06.031pubmed: 40607117google scholar: lookup
            2. Nagelli CV, Evans CH, De la Vega RE. Gene Delivery to Chondrocytes. Adv Exp Med Biol 2023;1402:95-105.
              doi: 10.1007/978-3-031-25588-5_7pubmed: 37052849google scholar: lookup
            3. Wang Y, Chen Y, Wei Y. Osteoarthritis animal models for biomaterial-assisted osteochondral regeneration. Biomater Transl 2022;3(4):264-279.
              doi: 10.12336/biomatertransl.2022.04.006pubmed: 36846505google scholar: lookup
            4. Thampi P, Samulski RJ, Grieger JC, Phillips JN, McIlwraith CW, Goodrich LR. Gene therapy approaches for equine osteoarthritis. Front Vet Sci 2022;9:962898.
              doi: 10.3389/fvets.2022.962898pubmed: 36246316google scholar: lookup
            5. Watson-Levings RS, Palmer GD, Levings PP, Dacanay EA, Evans CH, Ghivizzani SC. Gene Therapy in Orthopaedics: Progress and Challenges in Pre-Clinical Development and Translation. Front Bioeng Biotechnol 2022;10:901317.
              doi: 10.3389/fbioe.2022.901317pubmed: 35837555google scholar: lookup
            6. Wu S, Guo W, Li R, Zhang X, Qu W. Progress of Platelet Derivatives for Cartilage Tissue Engineering. Front Bioeng Biotechnol 2022;10:907356.
              doi: 10.3389/fbioe.2022.907356pubmed: 35782516google scholar: lookup
            7. Evans CH, Ghivizzani SC, Robbins PD. Orthopaedic Gene Therapy: Twenty-Five Years On. JBJS Rev 2021 Aug 26;9(8).
              doi: 10.2106/JBJS.RVW.20.00220pubmed: 34437305google scholar: lookup
            8. Orth P, Eldracher M, Cucchiarini M, Madry H. Small-Diameter Subchondral Drilling Improves DNA and Proteoglycan Content of the Cartilaginous Repair Tissue in a Large Animal Model of a Full-Thickness Chondral Defect. J Clin Med 2020 Jun 18;9(6).
              doi: 10.3390/jcm9061903pubmed: 32570841google scholar: lookup
            9. Hakamivala A, Shuxin Li, Robinson K, Huang Y, Yu S, Yuan B, Borrelli J Jr, Tang L. Recruitment of endogenous progenitor cells by erythropoietin loaded particles for in situ cartilage regeneration. Bioact Mater 2020 Mar;5(1):142-152.
              doi: 10.1016/j.bioactmat.2020.01.007pubmed: 32072078google scholar: lookup
            10. Venkatesan JK, Rey-Rico A, Cucchiarini M. Current Trends in Viral Gene Therapy for Human Orthopaedic Regenerative Medicine. Tissue Eng Regen Med 2019 Aug;16(4):345-355.
              doi: 10.1007/s13770-019-00179-xpubmed: 31413939google scholar: lookup
            11. Cucchiarini M, Madry H. Biomaterial-guided delivery of gene vectors for targeted articular cartilage repair. Nat Rev Rheumatol 2019 Jan;15(1):18-29.
              doi: 10.1038/s41584-018-0125-2pubmed: 30514957google scholar: lookup
            12. Goodrich LR, Chen AC, Werpy NM, Williams AA, Kisiday JD, Su AW, Cory E, Morley PS, McIlwraith CW, Sah RL, Chu CR. Addition of Mesenchymal Stem Cells to Autologous Platelet-Enhanced Fibrin Scaffolds in Chondral Defects: Does It Enhance Repair?. J Bone Joint Surg Am 2016 Jan 6;98(1):23-34.
              doi: 10.2106/JBJS.O.00407pubmed: 26738900google scholar: lookup
            13. McIlwraith CW, Fortier LA, Frisbie DD, Nixon AJ. Equine Models of Articular Cartilage Repair. Cartilage 2011 Oct;2(4):317-26.
              doi: 10.1177/1947603511406531pubmed: 26069590google scholar: lookup
            14. Madry H, Orth P, Cucchiarini M. Gene Therapy for Cartilage Repair. Cartilage 2011 Jul;2(3):201-25.
              doi: 10.1177/1947603510392914pubmed: 26069580google scholar: lookup
            15. Evans CH, Huard J. Gene therapy approaches to regenerating the musculoskeletal system. Nat Rev Rheumatol 2015 Apr;11(4):234-42.
              doi: 10.1038/nrrheum.2015.28pubmed: 25776949google scholar: lookup
            16. Ortved KF, Begum L, Mohammed HO, Nixon AJ. Implantation of rAAV5-IGF-I transduced autologous chondrocytes improves cartilage repair in full-thickness defects in the equine model. Mol Ther 2015 Feb;23(2):363-73.
              doi: 10.1038/mt.2014.198pubmed: 25311491google scholar: lookup
            17. Madry H, Cucchiarini M. Tissue-engineering strategies to repair joint tissue in osteoarthritis: nonviral gene-transfer approaches. Curr Rheumatol Rep 2014 Oct;16(10):450.
              doi: 10.1007/s11926-014-0450-7pubmed: 25182678google scholar: lookup
            18. Evans C. Using genes to facilitate the endogenous repair and regeneration of orthopaedic tissues. Int Orthop 2014 Sep;38(9):1761-9.
              doi: 10.1007/s00264-014-2423-xpubmed: 25038968google scholar: lookup
            19. Gurusinghe S, Strappe P. Gene modification of mesenchymal stem cells and articular chondrocytes to enhance chondrogenesis. Biomed Res Int 2014;2014:369528.
              doi: 10.1155/2014/369528pubmed: 24963479google scholar: lookup
            20. Shui W, Yin L, Luo J, Li R, Zhang W, Zhang J, Huang W, Hu N, Liang X, Deng ZL, Hu Z, Shi LL, Luu HH, Haydon RC, He TC, Ho SH. Characterization of chondrocyte scaffold carriers for cell-based gene therapy in articular cartilage repair. J Biomed Mater Res A 2013 Dec;101(12):3542-50.
              doi: 10.1002/jbm.a.34661pubmed: 23629940google scholar: lookup
            21. Madry H, Kaul G, Zurakowski D, Vunjak-Novakovic G, Cucchiarini M. Cartilage constructs engineered from chondrocytes overexpressing IGF-I improve the repair of osteochondral defects in a rabbit model. Eur Cell Mater 2013 Apr 16;25:229-47.
              doi: 10.22203/ecm.v025a17pubmed: 23588785google scholar: lookup
            22. Santo VE, Gomes ME, Mano JF, Reis RL. Controlled release strategies for bone, cartilage, and osteochondral engineering--Part II: challenges on the evolution from single to multiple bioactive factor delivery. Tissue Eng Part B Rev 2013 Aug;19(4):327-52.
              doi: 10.1089/ten.TEB.2012.0727pubmed: 23249320google scholar: lookup
            23. Ng VY, Jump SS, Santangelo KS, Russell DS, Bertone AL. Genetic engineering of juvenile human chondrocytes improves scaffold-free mosaic neocartilage grafts. Clin Orthop Relat Res 2013 Jan;471(1):26-38.
              doi: 10.1007/s11999-012-2615-xpubmed: 23008026google scholar: lookup
            24. Longo UG, Petrillo S, Franceschetti E, Berton A, Maffulli N, Denaro V. Stem cells and gene therapy for cartilage repair. Stem Cells Int 2012;2012:168385.
              doi: 10.1155/2012/168385pubmed: 22481959google scholar: lookup
            25. Madry H, Cucchiarini M. Clinical potential and challenges of using genetically modified cells for articular cartilage repair. Croat Med J 2011 Jun;52(3):245-61.
              doi: 10.3325/cmj.2011.52.245pubmed: 21674822google scholar: lookup
            26. Payne KA, Lee HH, Haleem AM, Martins C, Yuan Z, Qiao C, Xiao X, Chu CR. Single intra-articular injection of adeno-associated virus results in stable and controllable in vivo transgene expression in normal rat knees. Osteoarthritis Cartilage 2011 Aug;19(8):1058-65.
              doi: 10.1016/j.joca.2011.04.009pubmed: 21571082google scholar: lookup
            27. Orth P, Kaul G, Cucchiarini M, Zurakowski D, Menger MD, Kohn D, Madry H. Transplanted articular chondrocytes co-overexpressing IGF-I and FGF-2 stimulate cartilage repair in vivo. Knee Surg Sports Traumatol Arthrosc 2011 Dec;19(12):2119-30.
              doi: 10.1007/s00167-011-1448-6pubmed: 21350959google scholar: lookup
            28. Chu CR, Szczodry M, Bruno S. Animal models for cartilage regeneration and repair. Tissue Eng Part B Rev 2010 Feb;16(1):105-15.
              doi: 10.1089/ten.TEB.2009.0452pubmed: 19831641google scholar: lookup
            29. Steinert AF, Proffen B, Kunz M, Hendrich C, Ghivizzani SC, Nöth U, Rethwilm A, Eulert J, Evans CH. Hypertrophy is induced during the in vitro chondrogenic differentiation of human mesenchymal stem cells by bone morphogenetic protein-2 and bone morphogenetic protein-4 gene transfer. Arthritis Res Ther 2009;11(5):R148.
              doi: 10.1186/ar2822pubmed: 19799789google scholar: lookup
            30. Goodrich LR, Choi VW, Carbone BA, McIlwraith CW, Samulski RJ. Ex vivo serotype-specific transduction of equine joint tissue by self-complementary adeno-associated viral vectors. Hum Gene Ther 2009 Dec;20(12):1697-702.
              doi: 10.1089/hum.2009.030pubmed: 19642864google scholar: lookup
            31. Evans CH, Ghivizzani SC, Robbins PD. Orthopedic gene therapy in 2008. Mol Ther 2009 Feb;17(2):231-44.
              doi: 10.1038/mt.2008.265pubmed: 19066598google scholar: lookup
            32. Neu CP, Komvopoulos K, Reddi AH. The interface of functional biotribology and regenerative medicine in synovial joints. Tissue Eng Part B Rev 2008 Sep;14(3):235-47.
              doi: 10.1089/ten.teb.2008.0047pubmed: 18601586google scholar: lookup
            33. Melrose J, Smith SM, Little CB, Moore RJ, Vernon-Roberts B, Fraser RD. Recent advances in annular pathobiology provide insights into rim-lesion mediated intervertebral disc degeneration and potential new approaches to annular repair strategies. Eur Spine J 2008 Sep;17(9):1131-48.
              doi: 10.1007/s00586-008-0712-zpubmed: 18584218google scholar: lookup
            34. Steinert AF, Nöth U, Tuan RS. Concepts in gene therapy for cartilage repair. Injury 2008 Apr;39 Suppl 1(Suppl 1):S97-113.
              doi: 10.1016/j.injury.2008.01.034pubmed: 18313477google scholar: lookup
            35. Chubinskaya S, Hurtig M, Rueger DC. OP-1/BMP-7 in cartilage repair. Int Orthop 2007 Dec;31(6):773-81.
              doi: 10.1007/s00264-007-0423-9pubmed: 17687553google scholar: lookup
            36. Cheng C, Conte E, Pleshko-Camacho N, Hidaka C. Differences in matrix accumulation and hypertrophy in superficial and deep zone chondrocytes are controlled by bone morphogenetic protein. Matrix Biol 2007 Sep;26(7):541-53.
              doi: 10.1016/j.matbio.2007.05.006pubmed: 17618099google scholar: lookup
            37. Steinert AF, Ghivizzani SC, Rethwilm A, Tuan RS, Evans CH, Nöth U. Major biological obstacles for persistent cell-based regeneration of articular cartilage. Arthritis Res Ther 2007;9(3):213.
              doi: 10.1186/ar2195pubmed: 17561986google scholar: lookup
            38. Koch TG, Heerkens T, Thomsen PD, Betts DH. Isolation of mesenchymal stem cells from equine umbilical cord blood. BMC Biotechnol 2007 May 30;7:26.
              doi: 10.1186/1472-6750-7-26pubmed: 17537254google scholar: lookup
            39. Madry H, Weimer A, Kohn D, Cucchiarini M. [Tissue engineering for articular cartilage repair improved by gene transfer. Current concepts]. Orthopade 2007 Mar;36(3):236-47.
              doi: 10.1007/s00132-007-1059-6pubmed: 17340098google scholar: lookup
            40. Jang JH, Bengali Z, Houchin TL, Shea LD. Surface adsorption of DNA to tissue engineering scaffolds for efficient gene delivery. J Biomed Mater Res A 2006 Apr;77(1):50-8.
              doi: 10.1002/jbm.a.30643pubmed: 16353173google scholar: lookup
            41. Evans CH, Ghivizzani SC, Gouze E, Rediske JJ, Schwarz EM, Robbins PD. The 3rd International Meeting on Gene Therapy in Rheumatology and Orthopaedics. Arthritis Res Ther 2005;7(6):273-8.
              doi: 10.1186/ar1853pubmed: 16277703google scholar: lookup
            42. Yoshikawa H, Myoui A. Bone tissue engineering with porous hydroxyapatite ceramics. J Artif Organs 2005;8(3):131-6.
              doi: 10.1007/s10047-005-0292-1pubmed: 16235028google scholar: lookup
            43. Ito H, Koefoed M, Tiyapatanaputi P, Gromov K, Goater JJ, Carmouche J, Zhang X, Rubery PT, Rabinowitz J, Samulski RJ, Nakamura T, Soballe K, O'Keefe RJ, Boyce BF, Schwarz EM. Remodeling of cortical bone allografts mediated by adherent rAAV-RANKL and VEGF gene therapy. Nat Med 2005 Mar;11(3):291-7.
              doi: 10.1038/nm1190pubmed: 15711561google scholar: lookup
            44. Seto H, Kamekura S, Miura T, Yamamoto A, Chikuda H, Ogata T, Hiraoka H, Oda H, Nakamura K, Kurosawa H, Chug UI, Kawaguchi H, Tanaka S. Distinct roles of Smad pathways and p38 pathways in cartilage-specific gene expression in synovial fibroblasts. J Clin Invest 2004 Mar;113(5):718-26.
              doi: 10.1172/JCI19899pubmed: 14991070google scholar: lookup
            45. Evans CH. Gene therapies for osteoarthritis. Curr Rheumatol Rep 2004 Feb;6(1):31-40.
              doi: 10.1007/s11926-004-0081-5pubmed: 14713400google scholar: lookup
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