Previous Article | Next Article ![]()
Molecular and Cellular Biology, June 1999, p. 4431-4442, Vol. 19, No. 6
Departamento de Bioquímica y
Biología Molecular1 and
Departamento de Morfología y Biología
Celular,2 Facultad de Medicina, Universidad de
Oviedo, 33006 Oviedo, Spain, and Department of Medicine
III, Osaka University Medical School, Suita, Osaka 565, Japan3
Received 27 July 1998/Returned for modification 8 September
1998/Accepted 8 March 1999
Collagenase 3 (MMP-13) is a recently identified member of the
matrix metalloproteinase (MMP) gene family that is expressed at high
levels in diverse human carcinomas and in articular cartilage from
arthritic patients. In addition to its expression in pathological conditions, collagenase 3 has been detected in osteoblasts and hypertrophic chondrocytes during fetal ossification. In this work, we
have evaluated the possibility that Cbfa1 (core binding factor 1), a
transcription factor playing a major role in the expression of
osteoblastic specific genes, is involved in the expression of
collagenase 3 during bone formation. We have functionally characterized a Cbfa motif present in the promoter region of collagenase 3 gene and
demonstrated, by cotransfection experiments and gel mobility shift
assays, that this element is involved in the inducibility of the
collagenase 3 promoter by Cbfa1 in osteoblastic and chondrocytic cells.
Furthermore, overexpression of Cbfa1 in osteoblastic cells unable to
produce collagenase 3 leads to the expression of this gene after
stimulation with transforming growth factor
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Collagenase 3 Is a Target of Cbfa1, a Transcription
Factor of the runt Gene Family Involved in Bone
Formation
. Finally, we show that
mutant mice deficient in Cbfa1, lacking mature osteoblasts but containing hypertrophic chondrocytes which are also a major source
of collagenase 3, do not express this protease during fetal development. These results provide in vivo evidence that collagenase 3 is a target of the transcriptional activator Cbfa1 in these cells. On
the basis of these transcriptional regulation studies, together with
the potent proteolytic activity of collagenase 3 on diverse collagenous
and noncollagenous bone and cartilage components, we proposed that this
enzyme may play a key role in the process of bone formation and remodeling.
*
Corresponding author. Mailing address: Departamento de
Bioquímica y Biología Molecular, Facultad de Medicina,
Universidad de Oviedo, 33006 Oviedo, Spain. Phone: 34-985-104201. Fax:
34-985-103564. E-mail: CLO{at}dwarf1.quimica.uniovi.es.
This article has been cited by other articles:
| J. Bacteriol. | J. Virol. | Eukaryot. Cell |
|---|
| Microbiol. Mol. Biol. Rev. | Clin. Vaccine Immunol. | All ASM Journals |
|---|