Gene interactions and pathways from curated databases and text-mining
Cells Tissues Organs 2008, PMID: 18354251

Notch1, Jagged1, and HES5 are abundantly expressed in osteoarthritis.

Karlsson, C; Brantsing, C; Egell, S; Lindahl, A

BACKGROUND

Notch signalling controls differentiation and proliferation in various cell types and is associated with several diseases. We investigated the localization and regulation of several Notch markers in human osteoarthritic (OA) cartilage as well as identified genes controlled by Notch signalling.

METHODS

Immunolocalization and real-time PCR analysis of Notch markers in healthy and OA articular cartilage were performed. Genes regulated by Notch signalling were studied using microarray. Cytokine-induced transcription of Notch markers was analyzed using real-time PCR and its effect on cellular localization of the intracellular domain of Notch1 (NICD1) was investigated using immunohistochemistry, subcellular fractionation, and transfection. The effect of NFkappaB activation on HES5 transcription was studied using the NFkappaB inhibitor pyrrolidine dithiocarbamate.

RESULTS

Notch signalling was activated in OA cartilage and Notch1, Jagged1, and HES5 were abundantly expressed compared to healthy cartilage. Notch signalling regulated the expression of several genes associated with OA, like interleukin-8, lubricin, CD10, matrix metalloproteinase-9, and bone morphogenetic protein-2. Cytokines significantly affected the expression of several Notch markers and repressed expression of HES5, but did not affect the cellular localization of NICD1.

CONCLUSIONS

Notch signalling is dysregulated in OA, inducing and repressing transcription of genes that could potentially partly contribute to the OA phenotype.

Diseases/Pathways annotated by Medline MESH: Osteoarthritis
Document information provided by NCBI PubMed

Text Mining Data

HES5 — NFkappaB: " The effect of NFkappaB activation on HES5 transcription was studied using the NFkappaB inhibitor pyrrolidine dithiocarbamate "

Manually curated Databases

No curated data.