Browse > Article
http://dx.doi.org/10.4196/kjpp.2020.24.3.249

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)
Publication Information
The Korean Journal of Physiology and Pharmacology / v.24, no.3, 2020 , pp. 249-257 More about this Journal
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.
Keywords
Apoptosis; Cholesterol; Chondrocytes; Osteoarthritis; 25-Hydroxycholesterol;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Cross M, Smith E, Hoy D, Nolte S, Ackerman I, Fransen M, Bridgett L, Williams S, Guillemin F, Hill CL, Laslett LL, Jones G, Cicuttini F, Osborne R, Vos T, Buchbinder R, Woolf A, March L. The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis. 2014;73:1323-1330.   DOI
2 Oliviero F, Lo Nigro A, Bernardi D, Giunco S, Baldo G, Scanu A, Sfriso P, Ramonda R, Plebani M, Punzi L. A comparative study of serum and synovial fluid lipoprotein levels in patients with various arthritides. Clin Chim Acta. 2012;413:303-307.   DOI
3 Kostopoulou F, Malizos KN, Papathanasiou I, Tsezou A. MicroRNA-33a regulates cholesterol synthesis and cholesterol efflux-related genes in osteoarthritic chondrocytes. Arthritis Res Ther. 2015;17:42.   DOI
4 Choi WS, Lee G, Song WH, Koh JT, Yang J, Kwak JS, Kim HE, Kim SK, Son YO, Nam H, Jin I, Park ZY, Kim J, Park IY, Hong JI, Kim HA, Chun CH, Ryu JH, Chun JS. The CH25H-CYP7B1-$ROR{\alpha}$ axis of cholesterol metabolism regulates osteoarthritis. Nature. 2019;566:254-258.   DOI
5 Olivier E, Dutot M, Regazzetti A, Laprevote O, Rat P. 25-Hydroxycholesterol induces both P2X7-dependent pyroptosis and caspasedependent apoptosis in human skin model: new insights into degenerative pathways. Chem Phys Lipids. 2017;207(Pt B):171-178.   DOI
6 Appukuttan A, Kasseckert SA, Kumar S, Reusch HP, Ladilov Y. Oxysterol-induced apoptosis of smooth muscle cells is under the control of a soluble adenylyl cyclase. Cardiovasc Res. 2013;99:734-742.   DOI
7 Trousson A, Bernard S, Petit PX, Liere P, Pianos A, El Hadri K, Lobaccaro JM, Ghandour MS, Raymondjean M, Schumacher M, Massaad C. 25-hydroxycholesterol provokes oligodendrocyte cell line apoptosis and stimulates the secreted phospholipase A2 type IIA via LXR beta and PXR. J Neurochem. 2009;109:945-958.   DOI
8 Farnaghi S, Crawford R, Xiao Y, Prasadam I. Cholesterol metabolism in pathogenesis of osteoarthritis disease. Int J Rheum Dis. 2017;20:131-140.   DOI
9 Wang JH, Tuohimaa P. Regulation of cholesterol 25-hydroxylase expression by vitamin D3 metabolites in human prostate stromal cells. Biochem Biophys Res Commun. 2006;345:720-725.   DOI
10 Honda A, Miyazaki T, Ikegami T, Iwamoto J, Maeda T, Hirayama T, Saito Y, Teramoto T, Matsuzaki Y. Cholesterol 25-hydroxylation activity of CYP3A. J Lipid Res. 2011;52:1509-1516.   DOI
11 Hwang HS, Kim HA. Chondrocyte apoptosis in the pathogenesis of osteoarthritis. Int J Mol Sci. 2015;16:26035-26054.   DOI
12 Perales S, Alejandre MJ, Palomino-Morales R, Torres C, Iglesias J, Linares A. Effect of oxysterol-induced apoptosis of vascular smooth muscle cells on experimental hypercholesterolemia. J Biomed Biotechnol. 2009;2009:456208.   DOI
13 Choi YK, Kim YS, Choi IY, Kim SW, Kim WK. 25-hydroxycholesterol induces mitochondria-dependent apoptosis via activation of glycogen synthase kinase-3beta in PC12 cells. Free Radic Res. 2008;42:544-553.   DOI
14 Travert C, Carreau S, Le Goff D. Induction of apoptosis by 25-hydroxycholesterol in adult rat Leydig cells: protective effect of 17betaestradiol. Reprod Toxicol. 2006;22:564-570.   DOI
15 Jang J, Park S, Jin Hur H, Cho HJ, Hwang I, Pyo Kang Y, Im I, Lee H, Lee E, Yang W, Kang HC, Won Kwon S, Yu JW, Kim DW. 25-Hydroxycholesterol contributes to cerebral inflammation of X-linked adrenoleukodystrophy through activation of the NLRP3 inflammasome. Nat Commun. 2016;7:13129.   DOI
16 Gold ES, Diercks AH, Podolsky I, Podyminogin RL, Askovich PS, Treuting PM, Aderem A. 25-Hydroxycholesterol acts as an amplifier of inflammatory signaling. Proc Natl Acad Sci U S A. 2014;111:10666-10671.   DOI
17 Diczfalusy U, Olofsson KE, Carlsson AM, Gong M, Golenbock DT, Rooyackers O, Flaring U, Bjorkbacka H. Marked upregulation of cholesterol 25-hydroxylase expression by lipopolysaccharide. J Lipid Res. 2009;50:2258-2264.   DOI
18 Reboldi A, Dang EV, McDonald JG, Liang G, Russell DW, Cyster JG. Inflammation. 25-Hydroxycholesterol suppresses interleukin-1-driven inflammation downstream of type I interferon. Science. 2014;345:679-684.   DOI
19 Liu Y, Wei Z, Ma X, Yang X, Chen Y, Sun L, Ma C, Miao QR, Hajjar DP, Han J, Duan Y. 25-Hydroxycholesterol activates the expression of cholesterol 25-hydroxylase in an LXR-dependent mechanism. J Lipid Res. 2018;59:439-451.   DOI
20 Cha E, Lee KM, Park KD, Park KS, Lee KW, Kim SM, Lee J. Hydroxycholesterol levels in the serum and cerebrospinal fluid of patients with neuromyelitis optica revealed by LC-Ag+CIS/MS/MS and LC-ESI/MS/MS with picolinic derivatization: increased levels and association with disability during acute attack. PLoS One. 2016;11:e0167819.   DOI