title: The critical role of UDP-galactose-4-epimerase in osteoarthritis: modulating proteoglycans synthesis of the articular chondrocytes.
abstract: UDP-galactose-4-epimerase (GALE) is a key enzyme catalyzing the interconversion of UDP-glucose and UDP-galactose, as well as UDP-N-acetylglucosamine and UDP-N-acetylgalactosamine, which are all precursors for the proteoglycans (PGs) synthesis. However, whether GALE is essential in cartilage homeostasis remains unknown. Therefore, we investigated the role of GALE in PGs synthesis of human articular chondrocytes, the GALE expression in OA, and the regulation of GALE expression by interleukin-1beta (IL-1β). Silencing GALE gene with specific siRNAs resulted in a markedly inhibition of PGs synthesis in human articular chondrocytes. GALE protein levels were also decreased in both human and rat OA cartilage, thus leading to losses of PGs contents. Moreover, GALE mRNA expression was stimulated by IL-1β in early phase, but suppressed in late phase, while the suppression of GALE expression induced by IL-1β was mainly mediated by stress-activated protein kinase/c-Jun N-terminal kinase pathway. These data indicated a critical role of GALE in maintaining cartilage homeostasis, and suggested that GALE inhibition might contribute to OA progress.
authors.affiliation: Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China. Electronic address: wenyinxian@whu.edu.cn.
authors.forename: Yinxian
authors.initials: Y
authors.lastname: Wen
authors.affiliation: Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China. Electronic address: heart.blue@163.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Qin
authors.affiliation: Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China. Electronic address: dy-198172@163.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China; Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071, China. Electronic address: wanghui19@whu.edu.cn.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: UMR 7365 CNRS-Nancy Université, Faculté de Médecine, Vandoeuvre-lès-Nancy, France. Electronic address: Jacques.Magdalou@univ-lorraine.fr.
authors.forename: Jacques
authors.initials: J
authors.lastname: Magdalou
authors.affiliation: Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071, China. Electronic address: lbchen@whu.edu.cn.
authors.forename: Liaobin
authors.initials: L
authors.lastname: Chen
mesh_terms: D000368:Aged; D002358:Cartilage, Articular / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007719:Knee Joint / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D020370:Osteoarthritis, Knee / Q000378:metabolism* / Q000473:pathology; D011509:Proteoglycans / Q000096:biosynthesis*; D014534:UDPglucose 4-Epimerase / Q000378:metabolism*
chemical_list: D011509:Proteoglycans; D014534:UDPglucose 4-Epimerase
keywords: Cartilage homeostasis; Interleukin-1beta; Osteoarthritis; Proteoglycan; UDP-galactose-4-epimerase