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Research for effect of irradiation on growth plate chondrocytes

辐射对生长板软骨细胞影响的研究

基本信息

批准号：
06454533
负责人：
FUCHIHATA Hajime
金额：
$ 4.16万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06454533/
关键词：
Growth-Plate Chondrocyte Irradiation

项目摘要

The retardation of bone growth caused by irradiation suggested to be closely related to the impairment of endochondral ossification in growth plate, but its mechanism remains unclear. In this study the direct effect of X-ray irradiation cytodifferentiation of the growth plate chondrocytes was examined using a rabbit growth plate chondrocyte culture system.1.One to 10Gy doses of X-ray to the chondrocytes in premature stage inhibited proteoglycan (PG) synthesis, and induced degradation of PG.A 10Gy dose of X-ray suppressed type X collagen synthesis and content without changing type II collagen expression, and decreased alkaline phosphatase (ALPase) activity. Calcium deposition in the extracellular matrix of 10Gy dose irradiated culture was 40% of the control. 2.A 10Gy dose of X-ray to the mature chondrocytes did not change PG synthesis. PG degradation, however, was enhanced after irradiation. Although 1 to 10Gy doses of X-ray did not affect type X collagen synthesis, suppressed ALPase activity and calcium deposition. 3.In the hypertrophic stage, 1 to 10Gy doses of irradiation had marginal effect on PG,type X collagen, and ALPase activity. However, [^<45>Ca] incorporation into the cell layr and calcium deposition were decreased. 4.The sensitivity of the cytodifferentiation of the chondrocytes to irradiation became less as their differentiation advanced.In this study we clarified that 1 to 10Gy doses of irradiation inhibited matrix formation, terminal differentiation and induction of extracellular matrix calcification of growth plate chondrocytes. However, once the chondrocytes were irradiated, they could not express the further differentiated phenotypes and the inhibitory effects of irradiation were never restored. These findings indicate that the disturbance of endochondral ossification by irradiation originate in the direct inhibitory effects of irradiation on the matrix synthesis and matrix calcification in growth plate chondrocytes.

放射性骨生长迟缓与生长板软骨内骨化障碍密切相关，但其机制尚不清楚。本研究采用兔生长板软骨细胞培养系统，观察X射线对生长板软骨细胞分化的直接影响：1. 1 ~ 10 Gy剂量的X射线对发育早期的软骨细胞蛋白多糖（PG）合成有抑制作用，并诱导PG降解; 10 Gy剂量的X射线对X型胶原合成和含量有抑制作用，而对II型胶原表达无影响;碱性磷酸酶（ALP）活性降低。10 Gy剂量照射培养物细胞外基质中钙沉积量为对照组的40%。2.10Gy剂量的X射线对软骨细胞PG合成无明显影响。PG降解，然而，增强照射后。1 ~ 10 Gy剂量的X射线虽然不影响X型胶原的合成，但抑制了ALP活性和钙沉积。3.1 ~ 10 Gy剂量照射对肥大期PG、X型胶原、ALP活性影响不大。然而，[^<45>Ca]掺入细胞层和钙沉积减少。4.随着软骨细胞分化程度的提高，其细胞分化对辐射的敏感性逐渐降低，本研究阐明1 ~ 10 Gy剂量的辐射抑制生长板软骨细胞的基质形成、终末分化和诱导细胞外基质钙化。然而，一旦软骨细胞被辐射，它们不能表达进一步分化的表型，并且辐射的抑制作用从未恢复。这些结果表明，辐射对软骨内骨化的干扰源于辐射对生长板软骨细胞基质合成和基质钙化的直接抑制作用。