Regulation of tenascin-C expression by tumor necrosis factor-alpha in cultured human osteoarthritis chondrocytes.
Expression of tenascin-C reappears in articular cartilage of persons with osteoarthritis (OA), while it is almost abolished in normal mature cartilage. Tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine, is upregulated in OA cartilage and is involved in the progression of OA, and stimulates tenascin-C expression in other types of cells. We investigated regulation of tenascin-C expression by TNF-alpha through nuclear factor-alphaB (NF-kappaB) in OA cartilage in vivo and in vitro.


METHODS
Human articular cartilages were obtained from patients with OA and immunofluorescence examination of tenascin-C and the activated RelA subunit was performed. Cultured chondrocytes isolated from human OA cartilage were treated with TNF-alpha and with SN50. Activation of RelA subunit of NF-kappaB was examined by immunolabeling. Changes in tenascin-C protein concentrations were determined by immunofluorescence of cells after monensin treatment and Western blot analysis of the cell lysates, and mRNA levels were analyzed by quantitative real-time polymerase chain reaction.


RESULTS
Increased intensity of tenascin-C staining was observed in the damaged cartilage compared with normal cartilage. Activated RelA staining in chondrocyte nuclei was prominent in tenascin-C-positive areas of OA cartilage. Treatment of cultured chondrocytes by TNF-alpha induced translocation of activated RelA to the nuclei, followed by upregulation of tenascin-C expression in both mRNA and protein. Treatment with SN50 inhibited increases of RelA and tenascin-C expression in chondrocytes.


CONCLUSIONS
TNF-alpha stimulated tenascin-C expression through NF-kappaB signaling with RelA activation in cultured OA chondrocytes, suggesting involvement of tenascin-C in OA cartilage remodeling.
Nakoshi
Yutaka
Y
Department of Orthopedic Surgery and Department of Pathology and Matrix Biology, Mie University Graduate School of Medicine, Mie, Japan.
Hasegawa
Masahiro
M
Sudo
Akihiro
A
Yoshida
Toshimichi
T
Uchida
Atsumasa
A
D000368:Aged; D000369:Aged, 80 and over; D002356:Cartilage / Q000503:physiopathology; D016022:Case-Control Studies; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D005269:Femur / Q000166:cytology; D006801:Humans; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism* / Q000503:physiopathology; D019063:Tenascin / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D015854:Up-Regulation
D019063:Tenascin; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha