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用钬-166氢氧化铁大颗粒进行放射性滑膜切除术后兔软骨基质的分析。

Analysis of lapine cartilage matrix after radiosynovectomy with holmium-166 ferric hydroxide macroaggregate.

作者信息

Mäkelä O T, Lammi M J, Uusitalo H, Hyttinen M M, Vuorio E, Helminen H J, Tulamo R-M

机构信息

Department of Clinical Veterinary Sciences, Faculty of Veterinary Medicine, PO Box 57, FIN-00014 University of Helsinki, Finland.

出版信息

Ann Rheum Dis. 2003 Jan;62(1):43-9. doi: 10.1136/ard.62.1.43.

Abstract

OBJECTIVE

To study the short and long term effects of radiosynovectomy on articular cartilage in growing and mature rabbits.

METHODS

The articular cartilage of the distal femurs of rabbits was examined four days, two months, and one year after radiosynovectomy with holmium-166 ferric hydroxide macroaggregate ([(166)Ho]FHMA). Arthritic changes were evaluated from histological sections by conventional and polarised light microscopy, and glycosaminoglycan measurements using safranin O staining, digital densitometry, and uronic acid determination. Proteoglycan synthesis was studied by metabolic [(35)]sulphate labelling followed by autoradiography, and electrophoretic analysis of extracted proteoglycans. Northern analyses were performed to determine the mRNA levels of type II collagen, aggrecan, and Sox9 in cartilage samples.

RESULTS

Radiosynovectomy had no major effect on the histological appearance of articular cartilage in mature rabbits, whereas more fibrillation was seen in [(166)Ho]FHMA radiosynovectomised knee joints of growing rabbits two months after treatment, but not after one year. Radiosynovectomy did not cause changes in the glycosaminoglycan content of cartilage or in the synthesis or chemical structure of proteoglycans. No radiosynovectomy related changes were seen in the mRNA levels of type II collagen, whereas a transient down regulation of aggrecan and Sox9 mRNA levels was seen in young rabbits two months after [(166)Ho]FHMA radiosynovectomy.

CONCLUSIONS

[(166)Ho]FHMA radiosynovectomy caused no obvious chondrocyte damage or osteoarthritic changes in mature rabbits, but in growing rabbits some transient radiation induced effects were seen--for example, mild cartilage fibrillation and down regulation of cartilage-specific genes.

摘要

目的

研究放射性滑膜切除对生长中和成熟家兔关节软骨的短期和长期影响。

方法

采用钬 - 166氢氧化铁大颗粒聚合体([(166)Ho]FHMA)对家兔进行放射性滑膜切除,分别于术后4天、2个月和1年检查股骨远端的关节软骨。通过常规和偏振光显微镜检查组织切片评估关节炎变化,并使用番红O染色、数字密度测定法和糖醛酸测定法测量糖胺聚糖。通过代谢性[(35)]硫酸盐标记后进行放射自显影以及对提取的蛋白聚糖进行电泳分析来研究蛋白聚糖的合成。进行Northern分析以确定软骨样品中II型胶原蛋白、聚集蛋白聚糖和Sox9的mRNA水平。

结果

放射性滑膜切除对成熟家兔关节软骨的组织学外观没有重大影响,而在生长中的家兔接受[(166)Ho]FHMA放射性滑膜切除术后2个月,膝关节出现更多的纤维化,但1年后未出现。放射性滑膜切除未引起软骨糖胺聚糖含量、蛋白聚糖合成或化学结构的变化。II型胶原蛋白的mRNA水平未见与放射性滑膜切除相关的变化,而在[(166)Ho]FHMA放射性滑膜切除术后2个月的幼兔中,聚集蛋白聚糖和Sox9的mRNA水平出现短暂下调。

结论

[(166)Ho]FHMA放射性滑膜切除对成熟家兔未造成明显的软骨细胞损伤或骨关节炎变化,但在生长中的家兔中观察到一些短暂的辐射诱导效应,例如轻度软骨纤维化和软骨特异性基因的下调。

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Sox9 is required for cartilage formation.软骨形成需要Sox9。
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