{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T19:57:21Z","timestamp":1792699041443,"version":"4.5.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2001,7,1]],"date-time":"2001-07-01T00:00:00Z","timestamp":993945600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2001,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Tumor necrosis factor \u03b1 (TNF-\u03b1) has been suggested to induce chondrocytic chondrolysis in both inflammatory and degenerative joint diseases. However, its intracellular signaling pathway leading to the chondrolysis has not been studied in detail. Thus, we investigated whether TNF-\u03b1 activates a transcription factor nuclear factor \u03baB (NF-\u03baB) in human chondrocyte-like cells (HCS-2\/8) and induces the expression of genes involved in the degradation of cartilage matrix. Treatment of the cells with TNF-\u03b1 markedly increased the levels of matrix metalloproteinase 1 (MMP-1), MMP-3, intercellular adhesion molecule 1 (ICAM-1), and cyclo-oxygenase 2 (COX-2) messenger RNAs (mRNAs). The increase in the mRNAs was associated with the activation of p65\/p50 heterodimer NF-\u03baB. I\u03baB-\u03b1 and I\u03baB-\u03b2, cytoplasmic molecules preventing the nuclear translocation of NF-\u03baB, were degraded rapidly by TNF-\u03b1 followed by their synthesis to the basal level. Treatment with proteasome inhibitors inhibited the degradation of both I\u03baB-\u03b1 and I\u03baB-\u03b2 and prevented the TNF-\u03b1-dependent nuclear translocation of p65. Furthermore, the inhibitors completely prevented the TNF-\u03b1-dependent induction of MMP-1, MMP-3, ICAM-1, and COX-2 mRNAs. Thus, it is shown that the activation of p65\/p50 NF-\u03baB by TNF-\u03b1 plays a cardinal role in inducing the expression of MMP-1, MMP-3, ICAM-1, and COX-2 genes, which are involved in matrix degradation and inflammatory reaction in chondrocytes, leading to chondrocytic chondrolysis.<\/jats:p>","DOI":"10.1359\/jbmr.2001.16.7.1272","type":"journal-article","created":{"date-parts":[[2006,4,27]],"date-time":"2006-04-27T00:29:33Z","timestamp":1146097773000},"page":"1272-1280","source":"Crossref","is-referenced-by-count":52,"title":["Tumor Necrosis Factor \u03b1 Induces Expression of Genes for Matrix Degradation in Human Chondrocyte-like HCS-2\/8 Cells Through Activation of NF-\u03baB: Abrogation of the Tumor Necrosis Factor \u03b1 Effect by Proteasome Inhibitors"],"prefix":"10.1093","volume":"16","author":[{"given":"Tadahiro","family":"Sakai","sequence":"first","affiliation":[{"name":"Department of Orthopedics, Nagoya University School of Medicine, Nagoya, Japan"},{"name":"Department of 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