Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Retinoic Acid Potentiates Nitric Oxide-Induced Dedifferentiation through the ERK Pathway in Rabbit Articular Chondrocytes

Retinoic acid의 ERK 신호전달경로를 통한 nitric oxide 유도 연골세포 탈분화 심화 기작

  • Yu, Seon-Mi (Department of Biological Sciences, College of Natural Sciences, Kongju National University) ;
  • Kim, Song-Ja (Department of Biological Sciences, College of Natural Sciences, Kongju National University)
  • 유선미 (국립공주대학교 자연과학대학 생명과학과) ;
  • 김송자 (국립공주대학교 자연과학대학 생명과학과)
  • Received : 2010.12.31
  • Accepted : 2011.03.26
  • Published : 2011.04.30
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Abstract

Retinoic acid (RA), a metabolite of vitamin A, is known to regulate dedifferentiation of rabbit articular chondrocytes. The regulatory mechanism of dedifferentiation by RA is not yet understood. Thus, the effect of RA on the regulation of nitric oxide (NO)-induced dedifferentiation was investigated in rabbit articular chondrocytes. RA caused loss of the differentiated chondrocyte phenotype as demonstrated by inhibition of type II collagen expression and proteoglycan synthesis. RA also accelerated NO-induced dedifferentiation in rabbit articular chondrocytes as detected by expression of type II collagen and Sox-9 using Western blot analysis and production of sulfated proteoglycan using Alcain blue staining. Further, RA potentiated NO-induced activation of ERK. Inhibition of ERK with PD98059 (PD) recovered the expression of type II collagen and Sox-9 and production of sulfate proteoglycan in NO-induced dedifferentiated chondrocytes by RA treatment. Our findings suggest that RA accelerates NO-induced dedifferentiation of rabbit articular chondrocytes via the ERK pathway.

Retinoic acid (RA)는 Vitamin A의 대사산물로서 토끼 관절 연골세포의 탈분화를 유도하는 물질로 알려져 있다. 그러나 RA가 탈분화를 조절하는 정확한 메커니즘은 잘 알려져 있지 않다. 따라서, Nitric Oxide (NO)가 유도하는 탈분화에 미치는 RA의 분자적 기전에 관한 연구를 수행하였다. 그 결과, RA는 NO가 유도하는 탈분화를 촉진시키는 것을 확인 할 수 있었다. 이와 같은 결과는 Western blot analysis를 통해 연골세포 분화의 표지 단백질인 type II collagen 및 Sox-9의 발현양상을 통해 확인 할 수 있었으며, Alcian blue staining을 통해 연골세포의 기질을 구성하고 있는 단백질인 sulfated proteoglycan의 발현량을 통해서도 확인 할 수 있었다. 또한, RA는 NO 가 유도하는 ERK의 활성을 더욱 증가 시켰다. ERK의 억제자인 PD98059를 사용하여 ERK의 활성을 억제하였을 때 RA가 감소시키는 type II collagen 및 Sox-9의 발현과 sulfated proteoglycan의 생성 양상이 PD98059에 의해 다시 회복되는 것을 확인 할 수 있었다. 이러한 모든 결과를 종합해 볼 때, RA는 NO가 유도하는 탈분화를 ERK 신호전달경로를 통해 조절하는 것을 확인 할 수 있었다.

Keywords

References

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