| RRC ID |
38492
|
| 著者 |
Smaldone S, Carta L, Ramirez F.
|
| タイトル |
Establishment of fibrillin-deficient osteoprogenitor cell lines identifies molecular abnormalities associated with extracellular matrix perturbation of osteogenic differentiation.
|
| ジャーナル |
Cell Tissue Res
|
| Abstract |
Fibrillin-1 and fibrillin-2 are structural components of the extracellular matrix which are also involved in modulating local TGFβ and BMP bioavailability. Loss of fibrillin-1 or fibrillin-2 is associated with perturbed osteoblast maturation principally as the result of unbalanced TGFβ and BMP signaling. Here, we demonstrated that stable expression of small hairpin RNAs against fibrillin-1(Fbn1) or fibrillin-2 (Fbn2) transcripts in the clonal osteoprogenitor cell line Kusa-A1 led to the same phenotypic and molecular manifestations as germline Fbn1- or Fbn2-null mutations in primary calvarial osteoblast cultures. Proof-of-concept experiments are also presented showing that Fbn1- or Fbn2-silenced Kusa-A1 cell lines are suitable models to identify candidate determinants of osteogenesis which are under the control of extracellular microfibrils. Specific findings included: the inference of a potential role for fibrillin-1-mediated cell-matrix interactions in regulating Kusa-A1 proliferation; the possibility of fibrillin-2 involvement in modulating the activity of transcription factor Runx2 by restricting microRNA expression and/or processing; and the suggestion that fibrillin-1 and fibrillin-2 influence Notch signaling indirectly by differentially regulating BMP signaling. Collectively, the data reiterated the notion that fibrillin-1 and fibrillin-2 exert opposite effects on osteoblast differentiation through the discrete modulation of a broad network of interacting signaling molecules.
|
| 巻・号 |
344(3)
|
| ページ |
511-7
|
| 公開日 |
2011-6-1
|
| DOI |
10.1007/s00441-011-1167-9
|
| PMID |
21538048
|
| PMC |
PMC3214762
|
| MeSH |
Animals
Cell Differentiation / physiology
Cell Line
Extracellular Matrix / metabolism*
Fibrillin-1
Fibrillin-2
Fibrillins
Mice
Microfilament Proteins / deficiency*
Microfilament Proteins / genetics
Microfilament Proteins / metabolism
Osteoblasts / cytology*
Osteoblasts / metabolism*
Signal Transduction
Transfection
|
| IF |
4.044
|
| 引用数 |
5
|
|
WOS 分野
|
CELL BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
KUSA-A1(RCB2081) |
