Impaired bone fracture healing in matrix metalloproteinase-13 deficient mice

Naoto Kosaki; Hironari Takaishi; Satoru Kamekura; Tokuhiro Kimura; Yasunori Okada; Li Minqi; Norio Amizuka; Ung il Chung; Kozo Nakamura; Hiroshi Kawaguchi; Yoshiaki Toyama; Jeanine D'Armiento

doi:10.1016/j.bbrc.2006.12.234

Impaired bone fracture healing in matrix metalloproteinase-13 deficient mice

Naoto Kosaki, Hironari Takaishi, Satoru Kamekura, Tokuhiro Kimura, Yasunori Okada, Li Minqi, Norio Amizuka, Ung il Chung, Kozo Nakamura, Hiroshi Kawaguchi, Yoshiaki Toyama, Jeanine D'Armiento

Research output: Contribution to journal › Article › peer-review

95 Citations (Scopus)

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.

Original language	English
Pages (from-to)	846-851
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	354
Issue number	4
DOIs	https://doi.org/10.1016/j.bbrc.2006.12.234
Publication status	Published - 2007 Mar 23
Externally published	Yes

Keywords

Angiogenesis
Chondroclast
Extracellular matrix
Fracture healing
MMP-13

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2006.12.234

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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.",

keywords = "Angiogenesis, Chondroclast, Extracellular matrix, Fracture healing, MMP-13",

author = "Naoto Kosaki and Hironari Takaishi and Satoru Kamekura and Tokuhiro Kimura and Yasunori Okada and Li Minqi and Norio Amizuka and Chung, {Ung il} and Kozo Nakamura and Hiroshi Kawaguchi and Yoshiaki Toyama and Jeanine D'Armiento",

note = "Funding Information: The authors thank Dr. K. Horiuchi and Dr. J. Takito for critical discussions. We are grateful to Dr. K. Hoshi for sharing his expertise on the chondrocyte culture system. This study was supported by the National Institute of Aging (AG016994) and the Grants-in-Aid provided by the Ministry of Education, Science and Culture, Japan for General Scientific Research and Scientific Research on Priority Areas; by the Uehara Foundation and the General Insurance Association of Japan.",

year = "2007",

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doi = "10.1016/j.bbrc.2006.12.234",

language = "English",

volume = "354",

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journal = "Biochemical and Biophysical Research Communications",

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T1 - Impaired bone fracture healing in matrix metalloproteinase-13 deficient mice

AU - Kosaki, Naoto

AU - Takaishi, Hironari

AU - Kamekura, Satoru

AU - Kimura, Tokuhiro

AU - Okada, Yasunori

AU - Minqi, Li

AU - Amizuka, Norio

AU - Chung, Ung il

AU - Nakamura, Kozo

AU - Kawaguchi, Hiroshi

AU - Toyama, Yoshiaki

AU - D'Armiento, Jeanine

N1 - Funding Information: The authors thank Dr. K. Horiuchi and Dr. J. Takito for critical discussions. We are grateful to Dr. K. Hoshi for sharing his expertise on the chondrocyte culture system. This study was supported by the National Institute of Aging (AG016994) and the Grants-in-Aid provided by the Ministry of Education, Science and Culture, Japan for General Scientific Research and Scientific Research on Priority Areas; by the Uehara Foundation and the General Insurance Association of Japan.

PY - 2007/3/23

Y1 - 2007/3/23

N2 - 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.

AB - 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.

KW - Angiogenesis

KW - Chondroclast

KW - Extracellular matrix

KW - Fracture healing

KW - MMP-13

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JF - Biochemical and Biophysical Research Communications

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ER -

Impaired bone fracture healing in matrix metalloproteinase-13 deficient mice

Abstract

Keywords

ASJC Scopus subject areas

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