Abstract
A vast number of long-noncoding RNAs (lncRNA) are found expressed in human cells, which RNAs have been developed along with human evolution. However, the physiological functions of these lncRNAs remain mostly unknown. In the present study, we for the first time uncovered the fact that one of such lncRNAs plays a significant role in the differentiation of chondrocytes and, possibly, of osteoblasts differentiated from mesenchymal stem cells, which cells eventually construct the human skeleton. The urothelial cancer-associated 1 (UCA1) lncRNA is known to be associated with several human malignancies. Firstly, we confirmed that UCA1 was expressed in normal human chondrocytes, as well as in a human chondrocytic cell line; whereas it was not detected in human bone marrow mesenchymal stem cells (hBMSCs). Of note, although UCA1 expression was undetectable in hBMSCs, it was markedly induced along with the differentiation toward chondrocytes, suggesting its critical role in chondrogenesis. Consistent with this finding, silencing of the UCA1 gene significantly repressed the expression of chondrogenic genes in human chondrocytic cells. UCA1 gene silencing and hyper-expression also had a significant impact on the osteoblastic phenotype in a human cell line. Finally, forced expression of UCA1 in a murine chondrocyte precursor, which did not possess a UCA1 gene, overdrove its differentiation into chondrocytes. These results indicate a physiological and important role of this lncRNA in the skeletal development of humans, who require more sustained endochondral ossification and osteogenesis than do smaller vertebrates.
| Original language | English |
|---|---|
| Pages (from-to) | 4825-4840 |
| Number of pages | 16 |
| Journal | Journal of Cellular Physiology |
| Volume | 233 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jun 1 2018 |
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Keywords
- chondrocytes
- lncRNA
- osteoblasts
- skeletogenesis
- UCA1
ASJC Scopus subject areas
- Physiology
- Clinical Biochemistry
- Cell Biology
Cite this
Physiological role of urothelial cancer-associated one long noncoding RNA in human skeletogenic cell differentiation. / Ishikawa, Takanori; Nishida, Takashi; Ono, Mitsuaki; Takarada, Takeshi; Nguyen, Ha Thi; Kurihara, Shinnosuke; Furumatsu, Takayuki; Murase, Yurika; Takigawa, Masaharu; Oohashi, Toshitaka; Kamioka, Hiroshi; Kubota, Satoshi.
In: Journal of Cellular Physiology, Vol. 233, No. 6, 01.06.2018, p. 4825-4840.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Physiological role of urothelial cancer-associated one long noncoding RNA in human skeletogenic cell differentiation
AU - Ishikawa, Takanori
AU - Nishida, Takashi
AU - Ono, Mitsuaki
AU - Takarada, Takeshi
AU - Nguyen, Ha Thi
AU - Kurihara, Shinnosuke
AU - Furumatsu, Takayuki
AU - Murase, Yurika
AU - Takigawa, Masaharu
AU - Oohashi, Toshitaka
AU - Kamioka, Hiroshi
AU - Kubota, Satoshi
PY - 2018/6/1
Y1 - 2018/6/1
N2 - A vast number of long-noncoding RNAs (lncRNA) are found expressed in human cells, which RNAs have been developed along with human evolution. However, the physiological functions of these lncRNAs remain mostly unknown. In the present study, we for the first time uncovered the fact that one of such lncRNAs plays a significant role in the differentiation of chondrocytes and, possibly, of osteoblasts differentiated from mesenchymal stem cells, which cells eventually construct the human skeleton. The urothelial cancer-associated 1 (UCA1) lncRNA is known to be associated with several human malignancies. Firstly, we confirmed that UCA1 was expressed in normal human chondrocytes, as well as in a human chondrocytic cell line; whereas it was not detected in human bone marrow mesenchymal stem cells (hBMSCs). Of note, although UCA1 expression was undetectable in hBMSCs, it was markedly induced along with the differentiation toward chondrocytes, suggesting its critical role in chondrogenesis. Consistent with this finding, silencing of the UCA1 gene significantly repressed the expression of chondrogenic genes in human chondrocytic cells. UCA1 gene silencing and hyper-expression also had a significant impact on the osteoblastic phenotype in a human cell line. Finally, forced expression of UCA1 in a murine chondrocyte precursor, which did not possess a UCA1 gene, overdrove its differentiation into chondrocytes. These results indicate a physiological and important role of this lncRNA in the skeletal development of humans, who require more sustained endochondral ossification and osteogenesis than do smaller vertebrates.
AB - A vast number of long-noncoding RNAs (lncRNA) are found expressed in human cells, which RNAs have been developed along with human evolution. However, the physiological functions of these lncRNAs remain mostly unknown. In the present study, we for the first time uncovered the fact that one of such lncRNAs plays a significant role in the differentiation of chondrocytes and, possibly, of osteoblasts differentiated from mesenchymal stem cells, which cells eventually construct the human skeleton. The urothelial cancer-associated 1 (UCA1) lncRNA is known to be associated with several human malignancies. Firstly, we confirmed that UCA1 was expressed in normal human chondrocytes, as well as in a human chondrocytic cell line; whereas it was not detected in human bone marrow mesenchymal stem cells (hBMSCs). Of note, although UCA1 expression was undetectable in hBMSCs, it was markedly induced along with the differentiation toward chondrocytes, suggesting its critical role in chondrogenesis. Consistent with this finding, silencing of the UCA1 gene significantly repressed the expression of chondrogenic genes in human chondrocytic cells. UCA1 gene silencing and hyper-expression also had a significant impact on the osteoblastic phenotype in a human cell line. Finally, forced expression of UCA1 in a murine chondrocyte precursor, which did not possess a UCA1 gene, overdrove its differentiation into chondrocytes. These results indicate a physiological and important role of this lncRNA in the skeletal development of humans, who require more sustained endochondral ossification and osteogenesis than do smaller vertebrates.
KW - chondrocytes
KW - lncRNA
KW - osteoblasts
KW - skeletogenesis
KW - UCA1
UR - http://www.scopus.com/inward/record.url?scp=85042529889&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85042529889&partnerID=8YFLogxK
U2 - 10.1002/jcp.26285
DO - 10.1002/jcp.26285
M3 - Article
C2 - 29150954
AN - SCOPUS:85042529889
VL - 233
SP - 4825
EP - 4840
JO - Journal of Cellular Physiology
JF - Journal of Cellular Physiology
SN - 0021-9541
IS - 6
ER -