RGD Reference Report - Structural and functional healing of critical-size segmental bone defects by transduced muscle-derived cells expressing BMP4. - Rat Genome Database

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Structural and functional healing of critical-size segmental bone defects by transduced muscle-derived cells expressing BMP4.

Authors: Shen, HC  Peng, H  Usas, A  Gearhart, B  Fu, FH  Huard, J 
Citation: Shen HC, etal., J Gene Med. 2004 Sep;6(9):984-91.
RGD ID: 9068399
Pubmed: PMID:15352071   (View Abstract at PubMed)
DOI: DOI:10.1002/jgm.588   (Journal Full-text)

BACKGROUND: Our previous studies have shown that muscle-derived cells, including a population of muscle stem cells, transduced with a retroviral vector expressing bone morphogenetic protein 4 (BMP4) can improve the healing of critical-size calvarial defects. However, we did not evaluate the functionality of the healed bone. The purpose of this study was to determine whether primary muscle-derived cells transduced with retroBMP4 can heal a long bone defect both structurally and functionally. METHODS: Primary muscle-derived cells were genetically engineered to express BMP4 and were implanted into 7-mm femoral defects created in syngeneic rats. Muscle-derived cells transduced with retroLacZ were used in the control group. Bone healing was monitored by radiography, histology, and biomechanical testing at designated time points. RESULTS: Most of the defects treated with muscle-derived cells expressing BMP4 formed bridging callous by 6 weeks after surgery, and exhibited radiographically evident union at 12 weeks after cell implantation. Histological analysis at 12 weeks revealed that the medullary canal of the femur was restored and the cortex was remodeled between the proximal and distal ends of each BMP4-treated defect. In contrast, the defects treated with muscle-derived cells expressing beta-galactosidase displayed nonunion at all tested time points. An evaluation of the maximum torque-to-failure in the treatment group indicated that the healed bones possessed 77 +/- 28% of the strength of the contralateral intact femora. Torsional stiffness and energy-to-failure were not significantly different between the treated and intact limbs. CONCLUSIONS: This study demonstrated that primary muscle-derived cells transduced with retroBMP4 can elicit both structural and functional healing of critical-size segmental long bone defects created in rats.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
BMP4HumanFemoral Fractures treatmentISOBmp4 (Rattus norvegicus) RGD 
Bmp4RatFemoral Fractures treatmentIDA  RGD 
Bmp4MouseFemoral Fractures treatmentISOBmp4 (Rattus norvegicus) RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Bmp4Ratpositive regulation of bone mineralization  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Bmp4  (bone morphogenetic protein 4)

Genes (Mus musculus)
Bmp4  (bone morphogenetic protein 4)

Genes (Homo sapiens)
BMP4  (bone morphogenetic protein 4)


Additional Information