한빛사논문
- 조회335
Gyuseok Lee, PhD1,2, Jiye Yang, MS3, Su-Jin Kim, MS1,2, Thanh-Tam Tran, PhD1,2, SunYoung Lee, PhD1, Ka Hyon Park, PhD1, Seung-Hee Kwon, MS1,2, Ki-Ho Chung, PhD4, Jeong-Tae Koh, PhD1,2, Yun Hyun Huh, PhD3, Jong-Keun Seon, MD5, Hyun Ah Kim, MD6, Jang-Soo Chun, PhD3, Je-Hwang Ryu, PhD1,2*
1Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, 61186, Republic of Korea.
2Hard-tissue Biointerface Research Center, School of Dentistry, Chonnam National University, Gwangju, 61186, Republic of Korea.
3School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, 61005, Republic of Korea.
4Department of Preventive and Public Health Dentistry, School of Dentistry, Chonnam National University, Gwangju, 61186, Republic of Korea.
5Department of Orthopedics, Chonnam National University Hwasun Hospital and Medical School, Hwasun, 58128, Republic of Korea.
6Department of Internal Medicine, Hallym University, Sacred Heart Hospital, Anyang, 14068, Republic of Korea.
*Corresponding Author: Je-Hwang Ryu, PhD, Professor
Abstract
Objectives: Osteoarthritis (OA) is the most common degenerative disease worldwide with no practical means of prevention and limited treatment options. Recently, our group unveiled a novel mechanism contributing to OA pathogenesis in association with abnormal cholesterol metabolism in chondrocytes. In this study, we aimed to establish a clinical link between lipid profiles and OA in humans, assess the effectiveness of cholesterol-lowering drugs in suppressing OA development in mice, and uncover the cholesterol-lowering mechanisms that effectively impede OA progression.
Methods: Five clinically approved cholesterol-lowering drugs (fenofibrate, atorvastatin, ezetimibe, niacin, and lomitapide) were injected into the knee joints or administered with diet to DMM-induced OA mice fed a 2% high-cholesterol diet. Gene expression linked to cholesterol metabolism were determined using microarray analysis. Furthermore, the in vivo functions of these genes were explored through intra-articular injection of either its inhibitor or adenovirus.
Results: Logistic regression analysis confirmed a close relationship between the diagnostic criteria of hyperlipidemia based on serum lipid levels and OA incidence. Among the cholesterol-lowering drugs examined, fenofibrate exerted the most significant protective effect against cartilage destruction, which was attributed to elevated levels of high-density lipoprotein cholesterol that is crucial for cholesterol efflux. Notably, cholesterol efflux was suppressed during OA progression via downregulation of apolipoprotein A1 binding protein (AIBP) expression. Overexpression of AIBP effectively inhibits OA progression.
Conclusions: Our results suggest that restoration of cholesterol homeostasis to a normal state through administration of fenofibrate or AIBP overexpression, both of which induce cholesterol efflux, offers an effective therapeutic option for OA.
논문정보
- Research article
- 2024년 09월 (BRIC 등록일 2024-09-13)
- 국내 연구진
- 의약학 > 분자세포의학
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