| RRC ID |
51634
|
| 著者 |
Saito M, Mulati M, Talib SZ, Kaldis P, Takeda S, Okawa A, Inose H.
|
| タイトル |
The Indispensable Role of Cyclin-Dependent Kinase 1 in Skeletal Development.
|
| ジャーナル |
Sci Rep
|
| Abstract |
Skeletal development is tightly regulated through the processes of chondrocyte proliferation and differentiation. Although the involvement of transcription and growth factors on the regulation of skeletal development has been extensively studied, the role of cell cycle regulatory proteins in this process remains elusive. To date, through cell-specific loss-of-function experiments in vivo, no cell cycle regulatory proteins have yet been conclusively shown to regulate skeletal development. Here, we demonstrate that cyclin-dependent kinase 1 (Cdk1) regulates skeletal development based on chondrocyte-specific loss-of-function experiments performed in a mouse model. Cdk1 is highly expressed in columnar proliferative chondrocytes and is greatly downregulated upon differentiation into hypertrophic chondrocytes. Cdk1 is essential for proper chondrocyte proliferation and deletion of Cdk1 resulted in accelerated differentiation of chondrocytes. In vitro and ex vivo analyses revealed that Cdk1 is an essential cell cycle regulatory protein for parathyroid hormone-related peptide (PTHrP) signaling pathway, which is critical to chondrocyte proliferation and differentiation. These results demonstrate that Cdk1 functions as a molecular switch from proliferation to hypertrophic differentiation of chondrocytes and thus is indispensable for skeletal development. Given the availability of inhibitors of Cdk1 activity, our results could provide insight for the treatment of diseases involving abnormal chondrocyte proliferation, such as osteoarthritis.
|
| 巻・号 |
6
|
| ページ |
20622
|
| 公開日 |
2016-2-10
|
| DOI |
10.1038/srep20622
|
| PII |
srep20622
|
| PMID |
26860366
|
| PMC |
PMC4816159
|
| MeSH |
Animals
Blotting, Western
Bone Development*
Bone and Bones / physiology*
CDC2 Protein Kinase / antagonists & inhibitors
CDC2 Protein Kinase / genetics
CDC2 Protein Kinase / metabolism*
Cell Differentiation
Cell Line
Cell Proliferation
Chondrocytes / cytology
Chondrocytes / metabolism
Chondrogenesis
Collagen Type II / metabolism
Collagen Type X / metabolism
In Situ Hybridization, Fluorescence
In Vitro Techniques
Mice
Mice, Knockout
Models, Animal
Parathyroid Hormone-Related Protein / metabolism
RNA Interference
RNA, Small Interfering / metabolism
Real-Time Polymerase Chain Reaction
Signal Transduction
Transfection
|
| IF |
3.998
|
| 引用数 |
5
|
| リソース情報 |
| ヒト・動物細胞 |
ATDC5(RCB0565) |
