Repository logo
 
Publication

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

2016-07Journal article Open Access
Simple item page
dc.contributor.authorCavaco, Sofia
dc.contributor.authorS B Viegas, Carla
dc.contributor.authorRafael, Marta S.
dc.contributor.authorRamos, Acacio
dc.contributor.authorMagalhes, Joana
dc.contributor.authorBlanco, Francisco J.
dc.contributor.authorVermeer, Cees
dc.contributor.authorSimes, D
dc.date.accessioned2017-04-07T15:57:06Z
dc.date.available2017-04-07T15:57:06Z
dc.date.issued2016-07
dc.description.abstractOsteoarthritis (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-1 beta results in an increased expression of COX2 and MMP13 and up-regulation of GRP. Importantly, while treatment of articular cells with gamma-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 gamma-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.
dc.identifier.doi10.1007/s00018-015-2033-9
dc.identifier.issn1420-682X
dc.identifier.issn1420-682X
dc.identifier.otherAUT: DSI00813;
dc.identifier.urihttp://hdl.handle.net/10400.1/9611
dc.language.isoeng
dc.peerreviewedyes
dc.relation.isbasedonWOS:000369535000010
dc.titleGla-rich protein is involved in the cross-talk between calcification and inflammation in osteoarthritis
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage1065
oaire.citation.issue5
oaire.citation.startPage1051
oaire.citation.titleCellular and Molecular Life Sciences
oaire.citation.volume73
person.familyNameViegas
person.familyNameRafael
person.familyNameSimes
person.givenNameCarla
person.givenNameMarta
person.givenNameDina
person.identifier.ciencia-idC414-F596-EEC6
person.identifier.ciencia-id1C10-BF17-0DD7
person.identifier.orcid0000-0002-5765-3665
person.identifier.orcid0000-0002-5518-9790
person.identifier.orcid0000-0002-5145-4753
person.identifier.ridN-6695-2014
person.identifier.ridN-2789-2014
person.identifier.scopus-author-id8656310300
person.identifier.scopus-author-id15078212800
person.identifier.scopus-author-id7201884723
rcaap.rightsopenAccess
rcaap.typearticle
relation.isAuthorOfPublication33984b3c-ffac-477a-896a-ddbf7aced4e3
relation.isAuthorOfPublicatione4c6f8da-c3f6-4eee-bf78-f023843c343b
relation.isAuthorOfPublication31bac96d-1d01-4b8f-8f2b-9da4be31ea41
relation.isAuthorOfPublication.latestForDiscoverye4c6f8da-c3f6-4eee-bf78-f023843c343b

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
H 9611 10.1007_s00018-015-2033-9.pdf
Size:
6.12 MB
Format:
Adobe Portable Document Format
Download

Collections

CCM2-Artigos (em revistas ou actas indexadas)