Comparative Effects of 2 Antioxidants, Selenomethionine and Epigallocatechin-Gallate, on Catabolic and Anabolic Gene Expression of Articular Chondrocytes

RINA ANDRIAMANALIJAONA, CATHERINE BAUGÉ, EMMANUELLE RENARD, FLORENCE LEGENDRE, MAHA RAOUDI, MADELEINE KYPRIOTOU, KARIM BOUMEDIENE, HUGUES GATTO, PATRICIA MONGINOUX, and JEAN-PIERRE PUJOL

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-kB (NF-kB) 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-1ß) 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-1ß, inducible nitric oxide synthase, cyclooxygenases (-1, -2), type II collagen and aggrecan, and transforming growth factor-ß (TGF-ß1, -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 µM Se-met prevented IL-1ß-induced MMP-1 and aggrecanase-1 expression, and reduced the cytokine inhibitory effect on type II collagen, aggrecan core protein, and TGF-ß receptor II (TGF-ßRII) mRNA levels. EGCg was more efficient in modulating the effects of IL-1ß on the genes studied. Whereas EGCg inhibited the IL-1ß-activated MAPK, NF-kB, and AP-1, Se-met stimulated that signaling pathway. This could account for the differential effects exerted by these antioxidants on chondrocytes.

Conclusion. 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. (J Rheumatol 2005;32:1958-67)

Key Indexing Terms:

SELENIUM
EPIGALLOCATECHIN-GALLATE
ANTIOXIDANTS
CHONDROCYTES
OSTEOARTHRITIS

---

From the Laboratory of Connective Tissue Biochemistry, Faculty of Medicine, Caen; and Virbac Laboratories, Carros, France.

Supported by Virbac Laboratories, Carros, France.

R. Andriamanalijaona, PhD; C. Baugé, Graduate; E. Renard, Graduate; F. Legendre, PhD; M. Raoudi, PhD; M. Kypriotou, PhD; K. Boumediene, PhD; J-P. Pujol, PhD, Laboratory of Connective Tissue Biochemistry, Faculty of Medicine, Caen; H. Gatto, PhD; P. Monginoux, PhD, Virbac Laboratories.

Address reprint requests to Dr. J-P. Pujol, Laboratory of Connective Tissue Biochemistry, Faculty of Medicine, 14032 Caen Cedex, France. E-mail: pujol@ibfa.unicaen.fr

Accepted for publication May 30, 2005.

---