본문 바로가기 대메뉴 바로가기
open
Close

Osteoarthritis Research Laboratory

Publication

Publication

대표논문

Nature 誌

작성자Osteoarthritis Research Laboratory  조회수1,126 등록일2019-02-20
그림2.png [1,273.3 KB]

 2019 Feb;566(7743):254-258. doi: 10.1038/s41586-019-0920-1. Epub 2019 Feb 6.

The CH25H-CYP7B1-RORα axis of cholesterol metabolism regulates osteoarthritis.

Abstract

Osteoarthritis-the most common form of age-related degenerative whole-joint disease1-is primarily characterized by cartilage destruction, as well as by synovial inflammation, osteophyte formation and subchondral bone remodelling2,3. However, the molecular mechanisms that underlie the pathogenesis of osteoarthritis are largely unknown. Although osteoarthritis is currently considered to be associated with metabolic disorders, direct evidence for this is lacking, and the role of cholesterol metabolism in the pathogenesis of osteoarthritis has not been fully investigated4-6. Various types of cholesterol hydroxylases contribute to cholesterol metabolism in extrahepatic tissues by converting cellular cholesterol to circulating oxysterols, which regulate diverse biological processes7,8. Here we show that the CH25H-CYP7B1-RORα axis of cholesterol metabolism in chondrocytes is a crucial catabolic regulator of the pathogenesis of osteoarthritis. Osteoarthritic chondrocytes had increased levels of cholesterol because of enhanced uptake, upregulation of cholesterol hydroxylases (CH25H and CYP7B1) and increased production of oxysterol metabolites. Adenoviral overexpression of CH25H or CYP7B1 in mouse joint tissues caused experimental osteoarthritis, whereas knockout or knockdown of these hydroxylases abrogated the pathogenesis of osteoarthritis. Moreover, retinoic acid-related orphan receptor alpha (RORα) was found to mediate the induction of osteoarthritis by alterations in cholesterol metabolism. These results indicate that osteoarthritis is a disease associated with metabolic disorders and suggest that targeting the CH25H-CYP7B1-RORα axis of cholesterol metabolism may provide a therapeutic avenue for treating osteoarthritis.

https://www.ncbi.nlm.nih.gov/pubmed/30728500

QUICK
MENU
GIST 대표GIST 대표 GIST PortalGIST Portal 생명과학부생명과학부 도서관도서관 증명서 발급증명서 발급