Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2003 Dec;197(3):356-69.
doi: 10.1002/jcp.10371.

TNFalpha suppresses link protein and type II collagen expression in chondrocytes: Role of MEK1/2 and NF-kappaB signaling pathways

Cheryle A Séguin  1 , Suzanne M Bernier
Affiliations

TNFalpha suppresses link protein and type II collagen expression in chondrocytes: Role of MEK1/2 and NF-kappaB signaling pathways

Cheryle A Séguin et al. J Cell Physiol. 2003 Dec.

Abstract

Tumor necrosis factor alpha (TNFalpha) inhibits matrix synthesis by chondrocytes in rheumatoid arthritis and osteoarthritis; however, the underlying signaling pathways are poorly characterized. This study investigated the TNFalpha-activated pathways regulating expression of two key components of the cartilage matrix-link protein and type II collagen. In rat articular chondrocytes, TNFalpha decreased link protein and type II collagen mRNA to undetectable levels within 48 h. Levels of link protein mRNA recovered more readily than type II collagen mRNA following removal of the cytokine. TNFalpha-mediated reduction in mRNA of both matrix molecules occurred at the level of transcription and, for link protein, mRNA stability. Turnover of type II collagen and link protein mRNA was dependent on new protein synthesis. In both prechondrocytes and articular chondrocytes, TNFalpha induced concentration-dependent activation of MEK1/2 and NF-kappaB, but not p38 or JNK. Sustained activation of NF-kappaB was observed for up to 72 h following continuous or transient exposure to TNFalpha. Using pharmacological and molecular approaches, the MEK1/2 and NF-kappaB pathways were found to mediate inhibition of type II collagen and link protein gene expression by TNFalpha. Both prechondrocytes and articular chondrocytes are targets of TNFalpha. This study identifies pathways through which TNFalpha perturbs the synthesis and organization of articular cartilage matrix during inflammation.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

MeSH terms

LinkOut - more resources