Complement C3 and C5 deficiency affects fracture healing
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Complement C3 and C5 deficiency affects fracture healing. / Ehrnthaller, Christian; Huber-Lang, Markus; Nilsson, Per; Bindl, Ronny; Redeker, Simon; Recknagel, Stefan; Rapp, Anna; Mollnes, Tom; Amling, Michael; Gebhard, Florian; Ignatius, Anita.
in: PLOS ONE, Jahrgang 8, Nr. 11, 01.01.2013, S. e81341.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Complement C3 and C5 deficiency affects fracture healing
AU - Ehrnthaller, Christian
AU - Huber-Lang, Markus
AU - Nilsson, Per
AU - Bindl, Ronny
AU - Redeker, Simon
AU - Recknagel, Stefan
AU - Rapp, Anna
AU - Mollnes, Tom
AU - Amling, Michael
AU - Gebhard, Florian
AU - Ignatius, Anita
PY - 2013/1/1
Y1 - 2013/1/1
N2 - There is increasing evidence that complement may play a role in bone development. Our previous studies demonstrated that the key complement receptor C5aR was strongly expressed in the fracture callus not only by immune cells but also by bone cells and chondroblasts, indicating a function in bone repair. To further elucidate the role of complement in bone healing, this study investigated fracture healing in mice in the absence of the key complement molecules C3 and C5. C3(-/-) and C5(-/-) as well as the corresponding wildtype mice received a standardized femur osteotomy, which was stabilized using an external fixator. Fracture healing was investigated after 7 and 21 days using histological, micro-computed tomography and biomechanical measurements. In the early phase of fracture healing, reduced callus area (C3(-/-): -25%, p=0.02; C5(-/-): -20% p=0.052) and newly formed bone (C3(-/-): -38%, p=0.01; C5(-/-): -52%, p=0.009) was found in both C3- and C5-deficient mice. After 21 days, healing was successful in the absence of C3, whereas in C5-deficient mice fracture repair was significantly reduced, which was confirmed by a reduced bending stiffness (-45%; p=0.029) and a smaller callus volume (-17%; p=0.039). We further demonstrated that C5a was activated in C3(-/-) mice, suggesting cleavage via extrinsic pathways. Our results suggest that the activation of the terminal complement cascade in particular may be crucial for successful fracture healing.
AB - There is increasing evidence that complement may play a role in bone development. Our previous studies demonstrated that the key complement receptor C5aR was strongly expressed in the fracture callus not only by immune cells but also by bone cells and chondroblasts, indicating a function in bone repair. To further elucidate the role of complement in bone healing, this study investigated fracture healing in mice in the absence of the key complement molecules C3 and C5. C3(-/-) and C5(-/-) as well as the corresponding wildtype mice received a standardized femur osteotomy, which was stabilized using an external fixator. Fracture healing was investigated after 7 and 21 days using histological, micro-computed tomography and biomechanical measurements. In the early phase of fracture healing, reduced callus area (C3(-/-): -25%, p=0.02; C5(-/-): -20% p=0.052) and newly formed bone (C3(-/-): -38%, p=0.01; C5(-/-): -52%, p=0.009) was found in both C3- and C5-deficient mice. After 21 days, healing was successful in the absence of C3, whereas in C5-deficient mice fracture repair was significantly reduced, which was confirmed by a reduced bending stiffness (-45%; p=0.029) and a smaller callus volume (-17%; p=0.039). We further demonstrated that C5a was activated in C3(-/-) mice, suggesting cleavage via extrinsic pathways. Our results suggest that the activation of the terminal complement cascade in particular may be crucial for successful fracture healing.
U2 - 10.1371/journal.pone.0081341
DO - 10.1371/journal.pone.0081341
M3 - SCORING: Journal article
C2 - 24260573
VL - 8
SP - e81341
JO - PLOS ONE
JF - PLOS ONE
SN - 1932-6203
IS - 11
ER -