Deterioration of fracture healing in the mouse model of NF1 long bone dysplasia.
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Deterioration of fracture healing in the mouse model of NF1 long bone dysplasia. / El Khassawna, T; Toben, Daniel; Kolanczyk, M; Schmidt-Bleek, K; Koennecke, I; Schell, H; Mundlos, S; Duda, G N.
In: BONE, Vol. 51, No. 4, 4, 2012, p. 651-660.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Deterioration of fracture healing in the mouse model of NF1 long bone dysplasia.
AU - El Khassawna, T
AU - Toben, Daniel
AU - Kolanczyk, M
AU - Schmidt-Bleek, K
AU - Koennecke, I
AU - Schell, H
AU - Mundlos, S
AU - Duda, G N
PY - 2012
Y1 - 2012
N2 - Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disease resulting from inactivating mutations in the gene encoding the protein neurofibromin. NF1 manifests as a heritable susceptibility to tumours of neural tissue mainly located in the skin (neurofibromas) and pigmented skin lesions. Besides these more common clinical manifestations, many NF1 patients (50%) have abnormalities of the skeleton. Long bones are often affected (usually the tibia) and the clinical signs range from bowing to spontaneous fractures and non-unions. Here we present the analysis of bone fracture healing in the Nf1(Prx1)-knock-out mouse, a model of NF1 long bone dysplasia. In line with previously reported cortical bone injury results, fracture healing was impaired in Nf1(Prx1) mice. We showed that the defective fracture healing in Nf1(Prx1) mice is characterized by diminished cartilaginous callus formation and a thickening of the periosteal bone. These changes are paralleled by fibrous tissue accumulation within the fracture site. We identify a population of fibrous tissue cells within the Nf1 deficient fracture as alpha-smooth muscle actin positive myofibroblasts. Additionally, histological and in-situ hybridization analysis reveal a direct contact of the fracture site with muscle fascia, suggesting a possible involvement of muscle derived cells in the fracture deterioration.
AB - Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disease resulting from inactivating mutations in the gene encoding the protein neurofibromin. NF1 manifests as a heritable susceptibility to tumours of neural tissue mainly located in the skin (neurofibromas) and pigmented skin lesions. Besides these more common clinical manifestations, many NF1 patients (50%) have abnormalities of the skeleton. Long bones are often affected (usually the tibia) and the clinical signs range from bowing to spontaneous fractures and non-unions. Here we present the analysis of bone fracture healing in the Nf1(Prx1)-knock-out mouse, a model of NF1 long bone dysplasia. In line with previously reported cortical bone injury results, fracture healing was impaired in Nf1(Prx1) mice. We showed that the defective fracture healing in Nf1(Prx1) mice is characterized by diminished cartilaginous callus formation and a thickening of the periosteal bone. These changes are paralleled by fibrous tissue accumulation within the fracture site. We identify a population of fibrous tissue cells within the Nf1 deficient fracture as alpha-smooth muscle actin positive myofibroblasts. Additionally, histological and in-situ hybridization analysis reveal a direct contact of the fracture site with muscle fascia, suggesting a possible involvement of muscle derived cells in the fracture deterioration.
KW - Animals
KW - Male
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Tomography, X-Ray Computed
KW - Actins/metabolism
KW - Disease Models, Animal
KW - Osteoblasts/pathology
KW - Genes, Neurofibromatosis 1
KW - Bone Diseases, Developmental/genetics/pathology
KW - Fracture Healing
KW - Tibia/pathology/radiography
KW - Animals
KW - Male
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Tomography, X-Ray Computed
KW - Actins/metabolism
KW - Disease Models, Animal
KW - Osteoblasts/pathology
KW - Genes, Neurofibromatosis 1
KW - Bone Diseases, Developmental/genetics/pathology
KW - Fracture Healing
KW - Tibia/pathology/radiography
M3 - SCORING: Journal article
VL - 51
SP - 651
EP - 660
JO - BONE
JF - BONE
SN - 8756-3282
IS - 4
M1 - 4
ER -