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


METHODS
Histological 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.


RESULTS
We 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.


CONCLUSIONS
Our data imply a role for PKC-δ in the osteochondral plasticity of the interface between articular cartilage and the osteochondral junction.
Guangzhou Institute of Traumatic Surgery, the Fourth Affiliated Hospital of Medical College, Jinan University, Guangzhou, 510220, China. dr.yang1192@yahoo.com.
Xiaohong
X
Yang
School of Pathology and Laboratory Medicine, University of Western Australia, Perth, WA, 6009, Australia. dian.teguh@research.uwa.edu.au.
Dian
D
Teguh
Department of Mechanical Engineering, Curtin University, Perth, WA, 6102, Australia. ping.wu@curtin.edu.au.
Jian-Ping
JP
Wu
School of Pathology and Laboratory Medicine, University of Western Australia, Perth, WA, 6009, Australia. bo.he@uwa.edu.au.|Present address: Harry Perkins Institute of Medical Research, The University of Western Australia, Nedlands, Perth, WA, 6009, Australia. bo.he@uwa.edu.au.
Bo
B
He
Department of Mechanical Engineering, Curtin University, Perth, WA, 6102, Australia. brett.kirk@curtin.edu.au.
Thomas Brett
TB
Kirk
Guangzhou Institute of Traumatic Surgery, the Fourth Affiliated Hospital of Medical College, Jinan University, Guangzhou, 510220, China. qinqinsn@163.com.
Shengnan
S
Qin
Guangzhou Institute of Traumatic Surgery, the Fourth Affiliated Hospital of Medical College, Jinan University, Guangzhou, 510220, China. drsmli@hotmail.com.
Siming
S
Li
Guangzhou Institute of Traumatic Surgery, the Fourth Affiliated Hospital of Medical College, Jinan University, Guangzhou, 510220, China. honghchen@21cn.com.
Honghui
H
Chen
Department of Biomedical Engineering, Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Jinan University, Guangzhou, 510632, China. weixue_jnu@aliyun.com.
Wei
W
Xue
School of Pathology and Laboratory Medicine, University of Western Australia, Perth, WA, 6009, Australia. 20217728@student.uwa.edu.au.
Benjamin
B
Ng
School of Pathology and Laboratory Medicine, University of Western Australia, Perth, WA, 6009, Australia. shek.chim@uwa.edu.au.
Shek Man
SM
Chim
School of Pathology and Laboratory Medicine, University of Western Australia, Perth, WA, 6009, Australia. Jennifer.tickner@uwa.edu.au.
Jennifer
J
Tickner
Guangzhou Institute of Traumatic Surgery, the Fourth Affiliated Hospital of Medical College, Jinan University, Guangzhou, 510220, China. jiake.xu@uwa.edu.au.|School of Pathology and Laboratory Medicine, University of Western Australia, Perth, WA, 6009, Australia. jiake.xu@uwa.edu.au.
Jiake
J
Xu
D000818:Animals; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology; D002358:Cartilage, Articular / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism / Q000473:pathology; D006025:Glycosaminoglycans / Q000378:metabolism; D006132:Growth Plate / Q000378:metabolism / Q000473:pathology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D010003:Osteoarthritis / Q000235:genetics / Q000378:metabolism*; D051745:Protein Kinase C-delta / Q000235:genetics / Q000378:metabolism*; D013194:Staining and Labeling / Q000379:methods
D006025:Glycosaminoglycans; D051745:Protein Kinase C-delta