A metaphyseal defect model of the femur for studies of murine bone healing

A bone defect model was developed in the distal metaphysis of the femur for studies on bone healing in the mouse. The circular defect involving 20% of the bone circumference resulted in a 34% reduction in the bending moment compared to intact bone. The healing process was followed using histomorphom...

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Bibliographic Details
Published in:Bone (New York, N.Y.) N.Y.), 2001-04, Vol.28 (4), p.423-429
Main Authors: Uusitalo, H, Rantakokko, J, Ahonen, M, Jämsä, T, Tuukkanen, J, KäHäri, V.-M, Vuorio, E, Aro, H.T
Format: Article
Language:English
Subjects:
Adenovirus
Animals
Biological and medical sciences
Biomechanical Phenomena
Biomechanical testing
Blotting, Northern
Bone healing
Female
Femoral Fractures - diagnostic imaging
Femoral Fractures - pathology
Femoral Fractures - physiopathology
Fracture Healing
Fundamental and applied biological sciences. Psychology
Gene therapy
Gene Transfer Techniques
Histomorphometry
Immunohistochemistry
Mice
Mice, Inbred C57BL
Models, Animal
Mouse
Peripheral quantitative computed tomography (pQCT)
RNA, Messenger - genetics
RNA, Messenger - metabolism
Skeleton and joints
Tomography, X-Ray Computed
Vertebrates: osteoarticular system, musculoskeletal system
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Summary:A bone defect model was developed in the distal metaphysis of the femur for studies on bone healing in the mouse. The circular defect involving 20% of the bone circumference resulted in a 34% reduction in the bending moment compared to intact bone. The healing process was followed using histomorphometry, peripheral quantitative computed tomography (pQCT), biomechanical testing, and molecular biological analyses. Histologically, healing of the defect was characterized by filling of the medullary cavity with trabecular new bone during the first week of healing, and by closing of the cortical window by 6 weeks. Small areas of periosteal chondrogenesis were frequently observed during defect healing. In pQCT, bone mineral content (BMC) of the defect area approached that of intact control bone already by 3 weeks, reflecting the production of trabecular bone. Similarly, the bending strength and stiffness of the healing femur reached the level of intact control femur already at 3 weeks. Bone formation and remodeling was followed by Northern analyses, which demonstrated elevated mRNA levels for bone components (type I collagen and osteocalcin), and for osteoclastic enzymes (cathepsin K, matrix metalloproteinase-9, and tartrate-resistant acid phosphatase) throughout the healing period. Finally, the applicability of the defect model for gene therapy experiments was tested using adenovirus-mediated transfer of the LacZ reporter gene. Both histochemistry and mRNA analyses demonstrated that the gene was expressed in the repair tissue with the highest expression during the first week of healing. The present model thus provides a standardized environment for studies on induction and remodeling of trabecular new bone in normal and genetically engineered mice.
ISSN:8756-3282
1873-2763
DOI:10.1016/S8756-3282(01)00406-9