Abstract
Tacrolimus (FK506) has been used as a therapeutic drug beneficial for the treatment of rheumatoid arthritis in humans. In this study, we investigated the effects of FK506 on cellular differentiation in cultured chondrogenic cells. Culture with FK506 led to a significant and concentration-dependent increase in Alcian blue staining for matrix proteoglycan at 0.1 to 1,000 ng /ml, but not in alkaline phosphatase (ALP) activity, in ATDC5 cells, a mouse pre- chondrogenic cell line, cultured for 7 to 28 days, while the non-steroidal anti-inflammatory drug indomethacin significantly decreased Alcian blue staining in a concentration-dependent manner, without altering ALP activity. FK506 significantly increased the expression of mRNA for both type II and type X collagen, but not for osteopontin, in ATDC5 cells. Similar promotion was seen in chondrogenic differentiation in both mouse metatarsals and chondrocytes cultured with FK506. However, FK506 failed to significantly affect transcriptional activity of the reporter construct for either sry-type HMG box 9 (Sox9) or runt-related transcription factor-2 (Runx2), which are both transcription factors responsible for chondrocytic maturation as a master regulator. These results suggest that FK506 may predominantly promote cellular differentiation into proliferating chondrocytes through a mechanism not relevant to the transactivation by either Sox9 or Runx2 in chondrogenic cells.
| Original language | English |
|---|---|
| Pages (from-to) | 413-423 |
| Number of pages | 11 |
| Journal | Journal of Pharmacological Sciences |
| Volume | 109 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2009 |
| Externally published | Yes |
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Keywords
- ATDC5 cell
- Chondrocyte
- Metatarsal
- Tacrolimus
- Type II collagen
ASJC Scopus subject areas
- Pharmacology
- Molecular Medicine
Cite this
Predominant promotion by tacrolimus of chondrogenic differentiation to proliferating chondrocytes. / Nakamura, Yukari; Takarada, Takeshi; Kodama, Ayumi; Hinoi, Eiichi; Yoneda, Yukio.
In: Journal of Pharmacological Sciences, Vol. 109, No. 3, 2009, p. 413-423.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Predominant promotion by tacrolimus of chondrogenic differentiation to proliferating chondrocytes
AU - Nakamura, Yukari
AU - Takarada, Takeshi
AU - Kodama, Ayumi
AU - Hinoi, Eiichi
AU - Yoneda, Yukio
PY - 2009
Y1 - 2009
N2 - Tacrolimus (FK506) has been used as a therapeutic drug beneficial for the treatment of rheumatoid arthritis in humans. In this study, we investigated the effects of FK506 on cellular differentiation in cultured chondrogenic cells. Culture with FK506 led to a significant and concentration-dependent increase in Alcian blue staining for matrix proteoglycan at 0.1 to 1,000 ng /ml, but not in alkaline phosphatase (ALP) activity, in ATDC5 cells, a mouse pre- chondrogenic cell line, cultured for 7 to 28 days, while the non-steroidal anti-inflammatory drug indomethacin significantly decreased Alcian blue staining in a concentration-dependent manner, without altering ALP activity. FK506 significantly increased the expression of mRNA for both type II and type X collagen, but not for osteopontin, in ATDC5 cells. Similar promotion was seen in chondrogenic differentiation in both mouse metatarsals and chondrocytes cultured with FK506. However, FK506 failed to significantly affect transcriptional activity of the reporter construct for either sry-type HMG box 9 (Sox9) or runt-related transcription factor-2 (Runx2), which are both transcription factors responsible for chondrocytic maturation as a master regulator. These results suggest that FK506 may predominantly promote cellular differentiation into proliferating chondrocytes through a mechanism not relevant to the transactivation by either Sox9 or Runx2 in chondrogenic cells.
AB - Tacrolimus (FK506) has been used as a therapeutic drug beneficial for the treatment of rheumatoid arthritis in humans. In this study, we investigated the effects of FK506 on cellular differentiation in cultured chondrogenic cells. Culture with FK506 led to a significant and concentration-dependent increase in Alcian blue staining for matrix proteoglycan at 0.1 to 1,000 ng /ml, but not in alkaline phosphatase (ALP) activity, in ATDC5 cells, a mouse pre- chondrogenic cell line, cultured for 7 to 28 days, while the non-steroidal anti-inflammatory drug indomethacin significantly decreased Alcian blue staining in a concentration-dependent manner, without altering ALP activity. FK506 significantly increased the expression of mRNA for both type II and type X collagen, but not for osteopontin, in ATDC5 cells. Similar promotion was seen in chondrogenic differentiation in both mouse metatarsals and chondrocytes cultured with FK506. However, FK506 failed to significantly affect transcriptional activity of the reporter construct for either sry-type HMG box 9 (Sox9) or runt-related transcription factor-2 (Runx2), which are both transcription factors responsible for chondrocytic maturation as a master regulator. These results suggest that FK506 may predominantly promote cellular differentiation into proliferating chondrocytes through a mechanism not relevant to the transactivation by either Sox9 or Runx2 in chondrogenic cells.
KW - ATDC5 cell
KW - Chondrocyte
KW - Metatarsal
KW - Tacrolimus
KW - Type II collagen
UR - http://www.scopus.com/inward/record.url?scp=67249116668&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67249116668&partnerID=8YFLogxK
U2 - 10.1254/jphs.08315FP
DO - 10.1254/jphs.08315FP
M3 - Article
C2 - 19270431
AN - SCOPUS:67249116668
VL - 109
SP - 413
EP - 423
JO - Journal of Pharmacological Sciences
JF - Journal of Pharmacological Sciences
SN - 1347-8648
IS - 3
ER -