Abnormal expression of Col X, PTHrP, TGF-beta, bFGF, and VEGF in cartilage with Kashin-Beck disease.
The purpose of the current study was to investigate the abnormal expression of Col X, PTHrP, TGF-beta, bFGF, and VEGF in cartilage from patients with Kashin-Beck disease (KBD) to understand the pathogenesis of chondronecrosis in KBD. Articular cartilage and growth plate cartilage collected were divided into four groups: control children (8 samples, 5 cases), KBD children (19 samples, 9 cases), control adults (8 samples, 6 cases), and KBD adults (16 samples, 15 cases). The presence of PTHrP, TGF-beta1, bFGF, VEGF, and collagen X in articular cartilage and in growth plate cartilage was analyzed by immunohistochemistry. Articular cartilage and growth plate were each divided in three zones, and the rate of positive cells was counted by light microscope for cytoplasmic and pericellular staining. Results showed that (1) in KBD children, Col X expression was lower in the deep zone of growth plate cartilage than in normal children; in articular cartilage of KBD adults, however, collagen X expression was higher in the middle zone compared to the controls; (2) staining for bFGF, PTHrP, TGF-beta1, and VEGF in KBD adult patients was prominent in the chondrocyte clusters and the eroded surface of articular cartilage, and the percentage of chondrocyte staining was significantly higher than in control samples (t = 3.64-10.34, df = 12 for children and 19 for adults, P = 0.002-0.0001); and (3) the enhanced PTHrP, TGF-beta1, and VEGF staining in the deep and middle zone of KBD articular cartilage correlated with the high incidence of chondronecrosis in the middle zone (48.5% +/- 10.2%) and deep zone (70.6% +/- 27.0%) of adult KBD cartilage. In conclusion, Col X expression was reduced in areas of chondrocyte necrosis in the deep zone of KBD articular cartilage, indicating changes in terminal chondrocyte differentiation. PTHrP, TGF-beta1, and VEGF expression was significantly altered and indicated degenerative changes in KBD cartilage, which initially resemble those occurring in osteoarthritis, but lead eventually to chondronecrosis, an event not observed in osteoarthritis.
Guo
Xiong
X
Institute of Endemic Diseases, Medical College of Xi'an Jiaotong University, No.76 Yanta West Road, Xi'an, Shannxi, 710061, China. guox@mail.xjtu.edu.cn
Zuo
Hong
H
Cao
Chun-Xia
CX
Zhang
Yan
Y
Geng
Dong
D
Zhang
Zeng-Tie
ZT
Zhang
Yin-Gang
YG
von der Mark
Klaus
K
von der Mark
Helga
H
D000328:Adult; D002356:Cartilage / Q000378:metabolism* / Q000473:pathology*; D002648:Child; D019902:Chondrocytes / Q000473:pathology; D003094:Collagen / Q000235:genetics*; D005260:Female; D005346:Fibroblast Growth Factors / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology; D044162:Parathyroid Hormone-Related Protein / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
D044162:Parathyroid Hormone-Related Protein; D016212:Transforming Growth Factor beta; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C108111:fibroblast growth factor 13; D005346:Fibroblast Growth Factors; D003094:Collagen