English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Tools annual

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Presents the access of premium content as premium feature

Premium Content

Global: Zendy Plus annual

Global: Zendy Free Plan

Irreversible cartilage collagen breakdown by the collagenolytic matrix metalloproteinases (MMPs)-1 and MMP-13 represents a key event in pathologies associated with tissue destruction such as arthritis. Inflammation is closely associated with such pathology and occurs in both rheumatoid and osteoarthritis making it highly relevant to the prevailing tissue damage that characterises these diseases. The inflammation-induced activating protein-1 (AP-1) transcription factor is an important regulator of both  MMP1  and  MMP13  genes with interplay between signalling pathways contributing to their expression. Here, we have examined the regulation of  MMP1  expression, and using  in vivo  chromatin immunoprecipitation analyses we have demonstrated that cFos bound to the AP-1  cis  element within the proximal  MMP1  promoter only when the gene was transcriptionally silent as previously observed for  MMP13 . Subsequent small interfering RNA-mediated silencing confirmed however, that cFos significantly contributes to  MMP1  expression. In contrast, silencing of  ATF3  (a prime  MMP13  modulator) did not affect  MMP1  expression whilst silencing of the Wnt-associated regulator cysteine- serine-rich nuclear protein-1 ( CSRNP1 ) resulted in substantial repression of  MMP1  but not  MMP13 . Furthermore, following an early transient peak in expression of CSRNP1 at the mRNA and protein levels similar to that seen for cFOS,  CSRNP1  expression subsequently persisted unlike cFOS. Finally, DNA binding assays indicated that the binding of CSRNP1 to the AP-1 consensus-like sequences within the proximal promoter regions of  MMP1  and  MMP13  was preferentially selective for  MMP1  whilst activating transcription factor 3 (ATF3) binding was exclusive to  MMP13 . These data further extend our understanding of the previously reported differential regulation of these MMP genes, and strongly indicate that although cFos modulates the expression of  MMP1/13 , downstream factors such as CSRNP1 and ATF3 ultimately serve as transcriptional regulators in the context of an inflammatory stimulus for these potent collagenolytic MMPs.

Cytokine-induced cysteine- serine-rich nuclear protein-1 (CSRNP1) selectively contributes to MMP1 expression in human chondrocytes