[Characterization of biologic behaviors and cDNA expression of articular chondrocytes in spondyloepiphyseal dysplasia tarda with progressive arthropathy].
OBJECTIVE
Spondyloepiphyseal dysplasia tarda with progressive arthropathy (SEDT-PA) is an autosomal-recessive hereditary disorder of cartilage homeostasis. The pathogenesis of SEDT-PA is unknown though it has been demonstrated that CCN6 is the SEDT-PA causing gene. The present study characterized the biologic behaviors and cDNA differential expression profile of articular chondrocytes in SEDT-PA.


METHODS
The morphologic and functional features of growth, proliferation, differentiation and DNA synthesis of SEDT-PA chondrocytes were determined with cell growth curve, (3)H-TDR incorporation, MTT and flow cytometry. cDNA differential expression profile was carried out with gene microarray containing 8000 genes. Differentially expressed genes were verified by RT-PCR, Western blot and immunohistochemistry.


RESULTS
As compared with normal control, the variant chondrocytes were much larger in size with an enhanced ability of proliferation and DNA synthesis and increased ratio of G(2)-M (10.72% vs 0.11%) to S phases (37.0% vs 15.8%). Matrix metalloproteinases (MMPs), which decompose the extra-cellular matrix of the cartilage, accumulated at the endochylema and failed in exocytosis, which lead to the negative feedback of the mRNA transcriptions. The mRNA expression of MMPs was down-regulated. At the same time, the mRNA expression of genes related to cell growth, proliferation and progression of cell cycles were up-regulated, while most of those associated with extracellular matrix, non-collagen proteins and poly-proteoglycans were down-regulated.


CONCLUSIONS
The accumulation and failure in exocytosis of the MMPs decompose the extra-cellular matrix of the cartilage. The decreased expression of matrix proteins and polyproteoglycans is involved in the pathogenesis of arthropathy resulted from CCN6 mutation.
Zhou
Hou-de
HD
Institute of Endocrinology and Metabolism, the Second Xiangya Hospital of Central South University, Changsha 410011, China.
Peng
Yi-Qun
YQ
Gu
Wei
W
Li
Jian
J
Xie
Hui
H
Liu
Min
M
Luo
Xiang-Hang
XH
Huang
Qiu-Xia
QX
Guo
Li-Juan
LJ
Yuan
Ling-Qing
LQ
Ni
Jiang-Dong
JD
Zhang
Xiang-Sheng
XS
Liao
Er-Yuan
EY
D000328:Adult; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism / Q000502:physiology*; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007592:Joint Diseases / Q000378:metabolism / Q000473:pathology*; D010009:Osteochondrodysplasias / Q000378:metabolism / Q000473:pathology*; D015854:Up-Regulation