Impaired bone fracture healing in matrix metalloproteinase-13 deficient mice.
Vascular and cellular invasion into the cartilage is a critical step in the fracture healing. Matrix metalloproteinase-13 (MMP-13) is a member of the zinc-dependent endopeptidase family and plays an important role in remodeling of extracellular matrix. Therefore we investigated the possible involvement of MMP-13 in a murine model of stabilized bone fracture healing. Repair of the fracture in MMP-13 deficient (MMP-13(-/-)) mice was significantly delayed and characterized by a retarded cartilage resorption in the fracture callus. Immunohistochemistry indicated severe defects in vascular penetration and chondroclast recruitment to the fracture callus in MMP-13(-/-) mice. Consistent with the observations, the chondrocyte pellets cultured from the MMP13(-/-) mice exhibited diminished angiogenic activities when the pellets were co-cultured with endothelial cells. These results suggest that MMP-13 is crucial to the process of angiogenesis during healing of fracture, especially in the cartilage resorption process.
Kosaki
Naoto
N
Department of Orthopaedic Surgery, School of Medicine, Keio University, Tokyo, Japan.
Takaishi
Hironari
H
Kamekura
Satoru
S
Kimura
Tokuhiro
T
Okada
Yasunori
Y
Minqi
Li
L
Amizuka
Norio
N
Chung
Ung-Il
UI
Nakamura
Kozo
K
Kawaguchi
Hiroshi
H
Toyama
Yoshiaki
Y
D'Armiento
Jeanine
J
D000818:Animals; D002478:Cells, Cultured; D019902:Chondrocytes / Q000502:physiology; D017102:Fracture Healing / Q000502:physiology*; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000172:deficiency* / Q000502:physiology*; D051379:Mice; D018919:Neovascularization, Physiologic / Q000502:physiology; D013978:Tibial Fractures / Q000503:physiopathology
D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse