Protein kinase C delta null mice exhibit structural alterations in articular surface, intra-articular and subchondral compartments.

Xiaohong Yang,Dian Teguh,Wei Xue,Shek Man Chim,Honghui Chen,Jian-Ping Wu,Shengnan Qin,Thomas Brett Kirk,Bo He,Jiake Xu,Benjamin Ng,Jennifer Tickner,Siming Li

doi:10.1186/s13075-015-0720-4

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

Highlights

Structural 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) KO mice display atypical structural alterations at the articular cartilage and bone–cartilage interface Using histology with safranin O staining, we first observed a decreased safranin O staining in the articular cartilage surface in PKC-δ KO mice (Fig. 1d,e) as compared to WT mice (Fig. 1a,b)
We observed a thickening of articular cartilage and calcified bone–cartilage interface in the PKC-δ KO mice (Fig. 1d,e) as compared to those from WT mice (Fig. 1a,b)

Summary

Introduction

Structural 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. Genetic knockout (KO) studies have found that PKC-δ is involved in regulating B cell proliferation [7] and vein graft arteriosclerosis [8]. PKC-δ has been reported to play a part in bone and cartilage biology [9]. It regulates osteoclastic bone resorption [10,11,12] and embryonic bone formation [13]. Its role in articular cartilage and the bone–cartilage interface in adult mice is still not known

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