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 Plus annual

Presents the access of premium content as premium feature

Premium Content

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 Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

The present study examined the effect of C-type natriuretic peptide (CNP) on the anabolic and catabolic activities in chondrocyte/agarose constructs subjected to dynamic compression.    Methods  Constructs were cultured under free-swelling conditions or subjected to dynamic compression with low (0.1 to 100 p M ) or high concentrations (1 to 1,000 n M ) of CNP, interleukin-1β (IL-1β), and/or KT-5823 (inhibits cyclic GMP-dependent protein kinase II (PKGII)). Anabolic and catabolic activities were assessed as follows: nitric oxide (NO) and prostaglandin E 2  (PGE 2 ) release, and [ 3 H]-thymidine and  35 SO 4  incorporation were quantified by using biochemical assays. Gene expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), aggrecan, and collagen type II were assessed with real-time quantitative PCR (qPCR). Two-way ANOVA and the  post hoc  Bonferroni-corrected  t  tests were used to examine data.    Results  CNP reduced NO and PGE 2  release and partially restored [ 3 H]-thymidine and  35 SO 4  incorporation in constructs cultured with IL-1β. The response was dependent on the concentration of CNP, such that 100 p M  increased [ 3 H]-thymidine incorporation ( P  < 0.001). This is in contrast to  35 SO 4  incorporation, which was enhanced with 100 or 1000 n M  CNP in the presence and absence of IL-1β ( P  < 0.001). Stimulation by both dynamic compression and CNP and/or the PKGII inhibitor further reduced NO and PGE 2  release and restored [ 3 H]-thymidine and  35 SO 4  incorporation. In the presence and absence of IL-1β, the magnitude of stimulation for [ 3 H]-thymidine and  35 SO 4  incorporation by dynamic compression was dependent on the concentration of CNP and the response was inhibited with the PKGII inhibitor. In addition, stimulation by CNP and/or dynamic compression reduced IL-1β-induced iNOS and COX-2 expression and restored aggrecan and collagen type II expression. The catabolic response was not further influenced with the PKGII inhibitor in IL-1β-treated constructs.    Conclusions  Treatment with CNP and dynamic compression increased anabolic activities and blocked catabolic effects induced by IL-1β. The anabolic response was PKGII mediated and raises important questions about the molecular mechanisms of CNP with mechanical signals in cartilage. Therapeutic agents like CNP could be administered in conjunction with controlled exercise therapy to slow the OA disease progression and to repair damaged cartilage. The findings from this research provide the potential for developing novel agents to slow the pathophysiologic mechanisms and to treat OA in the young and old.

Biomechanical signals and the C-type natriuretic peptide counteract catabolic activities induced by IL-1β in chondrocyte/agarose constructs