Skip to Main content Skip to Navigation
Journal articles

Octacalcium phosphate crystals directly stimulate expression of inducible nitric oxide synthase through p38 and JNK mitogen-activated protein kinases in articular chondrocytes.

Abstract : Basic calcium phosphate (BCP) crystals, including hydroxyapatite, octacalcium phosphate (OCP) and carbonate-apatite, have been associated with severe osteoarthritis and several degenerative arthropathies. Most studies have considered the chondrocyte to be a bystander in the pathogenesis of calcium crystal deposition disease, assuming that synovial cell cytokines were the only triggers of chondrocyte activation. In the present study we identified direct activation of articular chondrocytes by OCP crystals, which are the BCP crystals with the greatest potential for inducing inflammation. OCP crystals induced nitric oxide (NO) production and inducible nitric oxide synthase (NOS) mRNA expression by isolated articular chondrocytes and cartilage fragments, in a dose-dependent manner and with variations over time. OCP crystals also induced IL-1beta mRNA expression. Using pharmacological and cytokine inhibitors, we observed that OCP crystals induced NO production and inducible NOS mRNA activation were regulated at both the transcriptional and the translational levels; were independent from IL-1beta gene activation; and involved p38 and c-Jun amino-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) pathways, as further confirmed by OCP crystal-induced p38 and JNK MAPK phosphorylation. Taken together, our data suggest that the transcriptional inducible NOS response to OCP crystals involved both the p38 and the JNK MAPK pathways, probably under the control of activator protein-1. NO, a major mediator of cartilage degradation, can be directly produced by BCP crystals in chondrocytes. Together with synovial activation, this direct mechanism may be important in the pathogenesis of destructive arthropathies triggered by microcrystals.
Complete list of metadatas

Cited literature [70 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-00090470
Contributor : Françoise Maylin <>
Submitted on : Thursday, August 31, 2006 - 2:32:55 PM
Last modification on : Saturday, March 28, 2020 - 2:15:44 AM
Long-term archiving on: : Tuesday, September 18, 2012 - 4:53:29 PM

Identifiers

Collections

Citation

Hang-Korng Ea, Benjamin Uzan, Christian Rey, Frédéric Lioté. Octacalcium phosphate crystals directly stimulate expression of inducible nitric oxide synthase through p38 and JNK mitogen-activated protein kinases in articular chondrocytes.. Arthritis Research and Therapy, BioMed Central, 2005, 7, pp.R915-26. ⟨10.1186/ar1763⟩. ⟨inserm-00090470⟩

Share

Metrics

Record views

290

Files downloads

523