Expression of metalloproteinase-13 (collagenase-3) is induced during fracture healing in mice

Yamagiwa, H; Tokunaga, Kunihiko; Hayami, Tadashi; Hatano, Hiroshi; Uchida, Motoyuki; Endo, Naoto; Takahashi, Hitoshi

doi:10.1016/s8756-3282(99)00157-x

Cited by 93 publications

(66 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Previous reports have described the contribution of MMP-13 to wound repair in several tissues, including bone, cornea, and joint tissue (21,22). However, the significance of MMP-13 in EC migration was still unknown.…”

Section: Discussionmentioning

confidence: 99%

Matrix metalloproteinase 13 mediates nitric oxide activation of endothelial cell migration

López-Rivera

Lizarbe

Martínez‐Moreno

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

To explore the mechanisms by which NO elicits endothelial cell (EC) migration we used murine and bovine aortic ECs in an in vitro wound-healing model. We found that exogenous or endogenous NO stimulated EC migration. Moreover, migration was significantly delayed in ECs derived from endothelial NO synthase-deficient mice compared with WT murine aortic EC. To assess the contribution of matrix metalloproteinase (MMP)-13 to NO-mediated EC migration, we used RNA interference to silence MMP-13 expression in ECs. Migration was delayed in cells in which MMP-13 was silenced. In untreated cells MMP-13 was localized to caveolae, forming a complex with caveolin-1. Stimulation with NO disrupted this complex and significantly increased extracellular MMP-13 abundance, leading to collagen breakdown. Our findings show that MMP-13 is an important effector of NO-activated endothelial migration.angiogenesis ͉ endothelium ͉ vasular remodeling W ound healing is an orchestrated cascade of enzymatic activities that converge toward damage repair. Wound healing involves inflammation and angiogenesis and is tightly regulated by cytokines (1). Vascular endothelial growth factor (VEGF) is a critical cytokine involved in angiogenesis, and nitric oxide (NO) is a downstream effector (2, 3). VEGF increases NO levels in endothelial cells (ECs) by activating endothelial NO synthase (eNOS͞NOS3) (4-7). Recently, the role of eNOS in EC migration has been demonstrated in vivo and in vitro (8, 9) but the precise mechanism by which NO regulates migration is unknown.ECs migrate as a result of an injury and during angiogenesis from preexisting vessels. The process is tightly regulated by matrix turnover, in which matrix metalloproteinases (MMPs) play a pivotal role (10-12). We have previously reported that NO induces MMP-13 expression and activity in bovine aortic ECs (BAECs) (13,14).MMPs are extracellular matrix-degrading endopeptidases. MMP expression and activity can be found in physiological and pathological situations, such as tissue development, atherosclerosis, ovarian function, arthritis, osteoarthritis, cancer, angiogenesis, and wound healing (15). MMP-13 was initially discovered in mammalian cell carcinomas and is also expressed by several cell types, including endothelium (13,(16)(17)(18).Here, we present evidence that MMP-13 is a downstream effector of NO-activated EC movement. We have developed a wound-healing model in BAECs and aortic cells from eNOS WT and eNOS-deficient mice. We show that aortic ECs lacking MMP-13 experience delayed migration, and aortic ECs from eNOS null mice present delayed cell migration and a significant decrease in MMP-13 expression. In addition, we present data showing that MMP-13 exists in association with caveolin-1 in resting cells, and that this complex is disrupted in the presence of NO, leading to the secretion of MMP-13 to the extracellular media. We postulate that NO induces EC movement in part via the disruption of the MMP-13͞caveolin-1 complex, which in turn releases the secretion of active MMP-13 to the ...

show abstract

Section: Discussionmentioning

confidence: 99%

Matrix metalloproteinase 13 mediates nitric oxide activation of endothelial cell migration

López-Rivera

Lizarbe

Martínez‐Moreno

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…We previously reported that the immature osteoblasts located at the interface between cartilage and bone express the mRNA for matrix metalloproteinase, which degrades the cartilage matrix in the callus. 13 Therefore, these immature osteoblasts are suitable targets for gene therapy designed to hasten matrix replacement. Here, as a step towards that goal, we demonstrated successful CAR-mediated gene transfer at a low dose of adenovirus to the site of fracture healing.…”

Section: Car In Fracture Healingmentioning

confidence: 99%

Coxsackievirus and adenovirus receptor (CAR)-positive immature osteoblasts as targets of adenovirus-mediated gene transfer for fracture healing

et al. 2003

Self Cite

View full text Add to dashboard Cite

“…MMPs 2, 8, 9, 13, and 14 have been shown to participate in the healing of bone fracture (Yamagiwa et al, 1999;Gerstenfeld et al, 2003;Henle et al, 2005;Wang et al, 2006). In contrast, information about involvement of MMPs in healing of bone defects is not available.…”

mentioning

confidence: 99%

Quantitative Analysis and Localization of mRNA Transcripts of Type I Collagen, Osteocalcin, MMP 2, MMP 8, and MMP 13 During Bone Healing in a Rat Calvarial Experimental Defect Model

Itagaki

Honma

Takahashi

et al. 2008

The Anatomical Record

View full text Add to dashboard Cite

The study examined the expression of matrix metalloproteinases (MMPs), type I collagen and osteocalcin during bone healing in a rat calvarial experimental defect model. Twelve-week-old male Wistar rats were used. A full-thickness standardized trephine defect was made in the parietal bone, with the rat under anesthesia. RNA was extracted from tissue that filled the original bone defect on days 1 and 3 and in weeks 1, 2, 3, 5, 8, 10, 12, 18, and 24 and processed for quantitative analysis of expression of type I collagen, osteocalcin and matrix metalloproteinases (MMPs) 2, 8, and 13 by using real-time polymerase chain reaction. Alternatively, the rats were fixed by perfusion through the aorta and resected calvaria were processed for in situ hybridization for these molecules. The expression of type I collagen, osteocalcin and MMPs 2 and 13 increased toward week 2 and decreased thereafter, whereas the expression of MMP 8 was the highest on day 1. The mRNA transcripts of type I collagen and osteocalcin were localized in osteoblasts and osteocytes, some of which expressed MMPs 2, 8, and 13. Osteoblasts and osteocytes may play a role in the remodeling of extracellular matrices with MMPs during healing of a defect in bone.

show abstract

Expression of metalloproteinase-13 (collagenase-3) is induced during fracture healing in mice

Cited by 93 publications

References 25 publications

Matrix metalloproteinase 13 mediates nitric oxide activation of endothelial cell migration

Matrix metalloproteinase 13 mediates nitric oxide activation of endothelial cell migration

Coxsackievirus and adenovirus receptor (CAR)-positive immature osteoblasts as targets of adenovirus-mediated gene transfer for fracture healing

Quantitative Analysis and Localization of mRNA Transcripts of Type I Collagen, Osteocalcin, MMP 2, MMP 8, and MMP 13 During Bone Healing in a Rat Calvarial Experimental Defect Model

Contact Info

Product

Resources

About