title: Comparative effects of 2 antioxidants, selenomethionine and epigallocatechin-gallate, on catabolic and anabolic gene expression of articular chondrocytes.
abstract: OBJECTIVE
  . To determine the effects of selenomethionine (Se-met) and epigallocatechin-gallate (EGCg) on gene expression, activation of mitogen-activating kinases, and DNA binding of nuclear factor-kappaB (NF-kappaB) and apolipoprotein-1 (AP-1) in articular chondrocytes.
  
  
  METHODS
  Chondrocytes, cultured in low-oxygen tension, were pretreated with L-selenomethionine or EGCg for 24 h, followed by interleukin 1 (IL-1beta) for 1 h (nuclear and cytoplasmic extracts) or 24 h (RNA extraction). Reverse transcription-polymerase chain reaction was performed to determine mRNA levels of matrix metalloproteinases (MMP-1, -3, -13), aggrecanases (-1, -2), IL-1beta, inducible nitric oxide synthase, cyclooxygenases (-1, -2), type II collagen and aggrecan, and transforming growth factor-beta (TGF-beta1, -2, -3) and their receptors I and II. Activity of mitogen-activating protein kinases (MAPK) was assayed by Western blot and AP-1/NF-kB DNA binding by electrophoretic mobility shift assay.
  
  
  RESULTS
  Pretreatment with 0.5 microM Se-met prevented IL-1beta-induced MMP-1 and aggrecanase-1 expression, and reduced the cytokine inhibitory effect on type II collagen, aggrecan core protein, and TGF-beta receptor II (TGF-betaRII) mRNA levels. EGCg was more efficient in modulating the effects of IL-1beta on the genes studied. Whereas EGCg inhibited the IL-1beta-activated MAPK, NF-kappaB, and AP-1, Se-met stimulated that signaling pathway. This could account for the differential effects exerted by these antioxidants on chondrocytes.
  
  
  CONCLUSIONS
  Our data provide insights into the mechanisms whereby ECGg and selenium modulate chondrocyte metabolism. Despite their differential mechanisms of action, the 2 compounds may exert global beneficial effects on articular cartilage.
authors.affiliation: Laboratory of Connective Tissue Biochemistry, Faculty of Medicine, 14032 Caen Cedex, France.
authors.forename: Rina
authors.initials: R
authors.lastname: Andriamanalijaona
authors.forename: Madeleine
authors.initials: M
authors.lastname: Kypriotou
authors.forename: Catherine
authors.initials: C
authors.lastname: Baugé
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Renard
authors.forename: Florence
authors.initials: F
authors.lastname: Legendre
authors.forename: Maha
authors.initials: M
authors.lastname: Raoudi
authors.forename: Karim
authors.initials: K
authors.lastname: Boumediene
authors.forename: Hugues
authors.initials: H
authors.lastname: Gatto
authors.forename: Patricia
authors.initials: P
authors.lastname: Monginoux
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Pujol
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004798:Enzymes / Q000235:genetics* / Q000378:metabolism; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D007375:Interleukin-1 / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012645:Selenomethionine / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D000975:Antioxidants; D004798:Enzymes; D007375:Interleukin-1; D016328:NF-kappa B; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D002392:Catechin; D004247:DNA; D012645:Selenomethionine; C045651:epigallocatechin gallate