title: Impaired bone fracture healing in matrix metalloproteinase-13 deficient mice.
abstract: 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.
authors.affiliation: Department of Orthopaedic Surgery, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Kosaki
authors.forename: Hironari
authors.initials: H
authors.lastname: Takaishi
authors.forename: Satoru
authors.initials: S
authors.lastname: Kamekura
authors.forename: Tokuhiro
authors.initials: T
authors.lastname: Kimura
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Okada
authors.forename: Li
authors.initials: L
authors.lastname: Minqi
authors.forename: Norio
authors.initials: N
authors.lastname: Amizuka
authors.forename: Ung-Il
authors.initials: UI
authors.lastname: Chung
authors.forename: Kozo
authors.initials: K
authors.lastname: Nakamura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawaguchi
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Toyama
authors.forename: Jeanine
authors.initials: J
authors.lastname: D'Armiento
mesh_terms: 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
chemical_list: D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse