Abnormal expression of Col X, PTHrP, TGF-β, bFGF, and VEGF in cartilage with Kashin-Beck disease
Abnormal expression of Col X, PTHrP, TGF-β, bFGF, and VEGF in cartilage with Kashin-Beck disease
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DOI：
10.1007/s00774-006-0690-3
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发表时间：
2006-07-01
影响因子：
3.3
通讯作者：
von der Mark, H
中科院分区：
文献类型：
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作者：
Guo, X;Zuo, H;von der Mark, H
本研究旨在探讨大骨节病（KBD）患者软骨中Col X、PTHrP、TGF-β、bFGF和VEGF的异常表达，以了解大骨节病软骨坏死的发病机制。采集的关节软骨和生长板软骨分为4组：对照组（8例，5例）、大骨节病组（19例，9例）、对照组（8例，6例）和大骨节病组（16例，15例）。通过免疫组化分析PTHrP、TGF-β 1、bFGF、VEGF和胶原X在关节软骨和生长板软骨中的存在。将关节软骨和生长板各分为三个区带，光镜下计数胞浆和细胞周染色阳性细胞的比率。结果显示：（1）大骨节病儿童生长板软骨深层X胶原表达低于正常儿童，成人关节软骨中层X胶原表达高于正常儿童;（2）bFGF、PTHrP、TGF-β（1）、而VEGF在成人大骨节病患者关节软骨细胞簇和关节软骨糜烂面中表达显著，软骨细胞染色百分比显著高于对照样品（t = 3.64-10.34，df = 12，成人19，P = 0.002-0.0001）;和（3）增强的PTHrP，TGF-β（1），大骨节病关节软骨深、中带VEGF染色阳性与软骨中带坏死发生率高相关软骨深层（48.5% ± 10.2%）和深层（70.6% ± 27.0%）。总之，在大骨节病关节软骨深层软骨细胞坏死区域，X型胶原表达减少，表明终末软骨细胞分化发生变化。PTHrP、TGF-β（1）和VEGF表达显著改变，表明大骨节病软骨发生退行性变化，最初类似于骨关节炎中发生的变化，但最终导致软骨坏死，这在骨关节炎中未观察到。
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-beta(1), 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-beta(1), 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-beta(1), 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-beta(1), 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.