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Home / Equine Research Bank / J Orthop Res / Acceleration of cartilage repair by genetically modified cho...
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

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