Dietary fat-associated osteoarthritic chondrocytes gain resistance to lipotoxicity through PKCK2/STAMP2/FSP27

Bone Research
Sung Won LeeYoung Hyun Yoo

Abstract

Free fatty acids (FFAs), which are elevated with metabolic syndrome, are considered the principal offender exerting lipotoxicity. Few previous studies have reported a causal relationship between FFAs and osteoarthritis pathogenesis. However, the molecular mechanism by which FFAs exert lipotoxicity and induce osteoarthritis remains largely unknown. We here observed that oleate at the usual clinical range does not exert lipotoxicity while oleate at high pathological ranges exerted lipotoxicity through apoptosis in articular chondrocytes. By investigating the differential effect of oleate at toxic and nontoxic concentrations, we revealed that lipid droplet (LD) accumulation confers articular chondrocytes, the resistance to lipotoxicity. Using high fat diet-induced osteoarthritis models and articular chondrocytes treated with oleate alone or oleate plus palmitate, we demonstrated that articular chondrocytes gain resistance to lipotoxicity through protein kinase casein kinase 2 (PKCK2)-six-transmembrane protein of prostate 2 (STAMP2)-and fat-specific protein 27 (FSP27)-mediated LD accumulation. We further observed that the exertion of FFAs-induced lipotoxicity was correlated with the increased concentration of cellular FFAs freed fr...Continue Reading

References

Sep 1, 1975·Arthritis and Rheumatism·W M BonnerM Bryant
Jun 1, 1991·Metabolism: Clinical and Experimental·L LippielloM Fienhold
Apr 1, 1987·Cell Biochemistry and Function·A M Nahir
Mar 1, 1995·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·J E Allende, C C Allende
Oct 23, 1997·Arthritis and Rheumatism·S HashimotoM Lotz
Mar 4, 2000·Proceedings of the National Academy of Sciences of the United States of America·Y T ZhouR H Unger
Sep 20, 2001·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·T AizawaL C Gerstenfeld
Mar 12, 2003·Proceedings of the National Academy of Sciences of the United States of America·Laura L ListenbergerJean E Schaffer
Aug 1, 1954·The Journal of Experimental Medicine·D W FAWCETT
Jul 9, 2004·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Ariel E FeldsteinGregory J Gores
Mar 12, 2009·Current Opinion in Lipidology·Jingyi GongPeng Li
Jul 9, 2009·Cell Metabolism·Rita T BrookheartJean E Schaffer
Oct 1, 2009·Arthritis and Rheumatism·Maryfran SowersJames A Ashton-Miller
Oct 22, 2009·American Journal of Physiology. Endocrinology and Metabolism·Kun LiuCynthia M Smas
Jun 3, 2011·The Journal of Clinical Investigation·Andrew S GreenbergDouglas G Mashek
Dec 20, 2011·American Journal of Physiology. Endocrinology and Metabolism·Matthew J WattRosalind A Coleman
Aug 22, 2012·Nature Reviews. Rheumatology·Qi ZhuoYan Wang
Oct 24, 2012·Current Opinion in Rheumatology·Francis BerenbaumXavier Houard
Oct 10, 2013·Journal of Microbiology and Biotechnology·Ran NohByoung Chul Park
Mar 20, 2014·International Journal of Biological Sciences·Seong Keun YooHye Young Kim
Sep 10, 2016·PloS One·Yoshinori AsouAtsushi Okawa

❮ Previous
Next ❯

Methods Mentioned

BETA
flow cytometry
confocal microscopy
light microscopy
transfection
protein assay

Software Mentioned

EXPO32 ADC XL
ZEN Blue

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis