2002 Fiscal Year Final Research Report Summary
The role of ets related gene (erg) in cartilage development
| Project/Area Number |
12470384
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Morphological basic dentistry
|
|---|
| Research Institution | Osaka University |
|---|
Principal Investigator |
OGAWA Yuzo Graduate School of Dentistry, Associate Professor, 大学院・歯学研究科, 助教授 (10135725)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
IWAMOTO Masahiro Graduate School of Dentistry, Assistant Professor, 大学院・歯学研究科, 助教授 (30223431)
HIGUCHI Yoshinobu Chugal Pharmaceutical, Reseach Laboratory, Chairman, 創薬研, 主査(研究職)
TOYOSAW Satoru Graduate School of Dentistry, Assistant Professor, 大学院・歯学研究科, 講師 (30243249)
IWAMOTO Motomi Grsduate School of Dentistry, Associate Profeasor, 大学院・歯学研究科, 講師 (80203644)
|
|---|
| Project Period (FY) |
2000 – 2002
|
| Keywords | chondrogenesis / growing cartilage / endochondral ossification / permanent cartilage / erg / transcription factor |
|---|
| Research Abstract |
During limb development, limb long bones are initially formed as histologically homegenous cartflagenous tissues. Later, chondroeytes in these tissues take two distinct developmental fates. Most of chondrocytes consist of bone shaft proliferate, synthesize cartilage-matrix, mature into hypertrophic cells, and finally disappear through the procese of endochondral ossification. However, chondrocytes present in longitudinal ends show relatively stable phenotype. These cells persist throughout life as permanent articular chondroeytes. Although maturation of trangient chondrocytes has been extensively studied, it is poorly understood how articular chondrocytes acquire/maintain stable phenotype and avoid maturation. We have previously identified C-1-1, a novel isoform of chick ets-related gene and showed that C-1-1 is preferentially expressed in developing articular cartilage. C-1-1 inhibits maturation and induced tenascin-C, a marker of immature/ articular cartilage in trangient chondrocytes. We next examined whether C-1-1 like +lecule is expressed and suppresses maturation in mammalian articular chondrocyte. Three mouse erg isoforms and 2 human erg isoforms were obtainsd by combination of RACE technique and cDNA library scleening. Each isoform was subuloned into RCASBP retrovirus vector and then introduced in primary chick embryo chondrocytes.
All of these isoforms suppressed chondrocytes maturation from moderate to severe extent. We also generated transgenic mice which over-express human ERG3(-81), possibiy orthologue of C-1-1, under the control of type II collagen promoter/enhancar. Chondrocytes maturation and endochondral bone formation was severely impaired in the transgenic mice. These findings strongly suggest that erg is involved not only in maintenance of articular chondrocytes phenotype but also regulates endochondral ossification by its anti-maturation activity.
|
