Predominant promotion by tacrolimus of chondrogenic differentiation to proliferating chondrocytes

Yukari Nakamura, Takeshi Takarada, Ayumi Kodama, Eiichi Hinoi, Yukio Yoneda

Research output: Contribution to journalArticle

25 Citations (Scopus)

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 languageEnglish
Pages (from-to)413-423
Number of pages11
JournalJournal of Pharmacological Sciences
Volume109
Issue number3
DOIs
Publication statusPublished - 2009
Externally publishedYes

Fingerprint

Tacrolimus
Chondrocytes
Alcian Blue
Alkaline Phosphatase
Transcription Factors
Collagen Type X
Staining and Labeling
Osteopontin
Metatarsal Bones
Collagen Type II
Proteoglycans
Indomethacin
Pharmaceutical Preparations
Transcriptional Activation
Cultured Cells
Rheumatoid Arthritis
Anti-Inflammatory Agents
Cell Line
Messenger RNA

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 journalArticle

Nakamura, Yukari ; Takarada, Takeshi ; Kodama, Ayumi ; Hinoi, Eiichi ; Yoneda, Yukio. / Predominant promotion by tacrolimus of chondrogenic differentiation to proliferating chondrocytes. In: Journal of Pharmacological Sciences. 2009 ; Vol. 109, No. 3. pp. 413-423.
@article{6ce5b057eb1a462788f4ce4651d8e58f,
title = "Predominant promotion by tacrolimus of chondrogenic differentiation to proliferating chondrocytes",
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.",
keywords = "ATDC5 cell, Chondrocyte, Metatarsal, Tacrolimus, Type II collagen",
author = "Yukari Nakamura and Takeshi Takarada and Ayumi Kodama and Eiichi Hinoi and Yukio Yoneda",
year = "2009",
doi = "10.1254/jphs.08315FP",
language = "English",
volume = "109",
pages = "413--423",
journal = "Journal of Pharmacological Sciences",
issn = "1347-8648",
publisher = "The Japanese Pharmacological Society",
number = "3",

}

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 -