Gla-rich protein is involved in the cross-talk between calcification and inflammation in osteoarthritis. | - CCMAR -

Journal Article

TitleGla-rich protein is involved in the cross-talk between calcification and inflammation in osteoarthritis.
Publication TypeJournal Article
AuthorsCavaco, S, Viegas, CSB, Rafael, MS, Ramos, A, Magalhães, J, Blanco, FJ, Vermeer, C, Simes, DC
Year of Publication2016
JournalCell Mol Life Sci
Date Published2016 Mar
KeywordsCalcinosis, Cell Differentiation, Cells, Cultured, Chondrocytes, Humans, Inflammation, Osteoarthritis, Proteins

Osteoarthritis (OA) is a whole-joint disease characterized by articular cartilage loss, tissue inflammation, abnormal bone formation and extracellular matrix (ECM) mineralization. Disease-modifying treatments are not yet available and a better understanding of osteoarthritis pathophysiology should lead to the discovery of more effective treatments. Gla-rich protein (GRP) has been proposed to act as a mineralization inhibitor and was recently shown to be associated with OA in vivo. Here, we further investigated the association of GRP with OA mineralization-inflammation processes. Using a synoviocyte and chondrocyte OA cell system, we showed that GRP expression was up-regulated following cell differentiation throughout ECM calcification, and that inflammatory stimulation with IL-1β results in an increased expression of COX2 and MMP13 and up-regulation of GRP. Importantly, while treatment of articular cells with γ-carboxylated GRP inhibited ECM calcification, treatment with either GRP or GRP-coated basic calcium phosphate (BCP) crystals resulted in the down-regulation of inflammatory cytokines and mediators of inflammation, independently of its γ-carboxylation status. Our results strengthen the calcification inhibitory function of GRP and strongly suggest GRP as a novel anti-inflammatory agent, with potential beneficial effects on the main processes responsible for osteoarthritis progression. In conclusion, GRP is a strong candidate target to develop new therapeutic approaches.


Alternate JournalCell. Mol. Life Sci.
PubMed ID26337479