The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Oxysterol 25-hydroxycholesterol as a metabolic pathophysiological factors of osteoarthritis induces apoptosis in primary rat chondrocytes

  • Seo, Yo-Seob (Department of Oral and Maxillofacial Radiology, School of Dentistry, Chosun University) ;
  • Cho, In-A (Institute of Dental Science, School of Dentistry, Chosun University) ;
  • Kim, Tae-Hyeon (Institute of Dental Science, School of Dentistry, Chosun University) ;
  • You, Jae-Seek (Department of Oral and Maxillofacial Surgery, School of Dentistry, Chosun University) ;
  • Oh, Ji-Su (Department of Oral and Maxillofacial Surgery, School of Dentistry, Chosun University) ;
  • Lee, Gyeong-Je (Department of Prosthodontics, School of Dentistry, Chosun University) ;
  • Kim, Do Kyung (Institute of Dental Science, School of Dentistry, Chosun University) ;
  • Kim, Jae-Sung (Institute of Dental Science, School of Dentistry, Chosun University)
  • Received : 2019.12.16
  • Accepted : 2020.02.26
  • Published : 2020.05.01
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Abstract

The aim of the present study was to investigate the pathophysiological etiology of osteoarthritis that is mediated by the apoptosis of chondrocytes exposed to 25-hydroxycholesterol (25-HC), an oxysterol synthesized by the expression of cholesterol-25-hydroxylase (CH25H) under inflammatory conditions. Interleukin-1β induced the apoptosis of chondrocytes in a dose- dependent manner. Furthermore, the production of 25-HC increased in the chondrocytes treated with interleukin-1β through the expression of CH25H. 25-HC decreased the viability of chondrocytes. Chondrocytes with condensed nucleus and apoptotic populations increased by 25-HC. Moreover, the activity and expression of caspase-3 were increased by the death ligand-mediated extrinsic and mitochondria-dependent intrinsic apoptotic pathways in the chondrocytes treated with 25-HC. Finally, 25-HC induced not only caspase-dependent apoptosis, but also induced proteoglycan loss in articular cartilage ex vivo cultured rat knee joints. These data indicate that 25-HC may act as a metabolic pathophysiological factor in osteoarthritis that is mediated by progressive chondrocyte death in the articular cartilage with inflammatory condition.

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References

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