Protein kinase C delta null mice exhibit structural alterations in articular surface, intra-articular and subchondral compartmentsReportar como inadecuado




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Arthritis Research and Therapy

, 17:210

First Online: 17 August 2015Received: 08 June 2015Accepted: 17 July 2015

Abstract

IntroductionStructural alterations in intra-articular and subchondral compartments are hallmarks of osteoarthritis, a degenerative disease that causes pain and disability in the aging population. Protein kinase C delta PKC-δ plays versatile functions in cell growth and differentiation, but its role in the articular cartilage and subchondral bone is not known.

MethodsHistological analysis including alcian blue, safranin O staining and fluorochrome labeling were used to reveal structural alterations at the articular cartilage surface and bone–cartilage interface in PKC-δ knockout KO mice. The morphology and organization of chondrocytes were studied using confocal microscopy. Glycosaminoglycan content was studied by micromass culture of chondrocytes of PKC-δ KO mice.

ResultsWe uncovered atypical structural demarcation between articular cartilage and subchondral bone of PKC-δ KO mice. Histology analyses revealed a thickening of the articular cartilage and calcified bone–cartilage interface, and decreased safranin O staining accompanied by an increase in the number of hypertrophic chondrocytes in the articular cartilage of PKC-δ KO mice. Interestingly, loss of demarcation between articular cartilage and bone was concomitant with irregular chondrocyte morphology and arrangement. Consistently, in vivo calcein labeling assay showed an increased intensity of calcein labeling in the interface of the growth plate and metaphysis in PKC-δ KO mice. Furthermore, in vitro culture of chondrocyte micromass showed a decreased alcian blue staining of chondrocyte micromass in the PKC-δ KO mice, indicative of a reduced level of glycosaminoglycan production.

ConclusionsOur data imply a role for PKC-δ in the osteochondral plasticity of the interface between articular cartilage and the osteochondral junction.

AbbreviationsDMEMDulbecco’s modified Eagle’s medium

FOLSCMFiber optic laser scanning confocal microscopy

KOKnockout

MAPKMitogen-activated protein kinase

MBIMaximum brightness image

MMAMethylmethacrylate

MMPMatrix metalloproteinase

NBFNeutral buffered formalin

OAOsteoarthritis

PBSPhosphate-buffered saline

PKC-δProtein kinase C delta

ROIRegion of interest

SDStandard deviation

TGF-βTransforming growth factor-beta

WTWild-type

Electronic supplementary materialThe online version of this article doi:10.1186-s13075-015-0720-4 contains supplementary material, which is available to authorized users.

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Autor: Xiaohong Yang - Dian Teguh - Jian-Ping Wu - Bo He - Thomas Brett Kirk - Shengnan Qin - Siming Li - Honghui Chen - Wei Xu

Fuente: https://link.springer.com/







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