Guenther H L, Guenther H E, Fleisch H
Biochem J. 1981 Apr 15;196(1):303-10. doi: 10.1042/bj1960303.
The effects in vivo of dichloromethanediphosphonate and 1-hydroxyethane 1,1-diphosphonate on collagen solubility, hydroxylation of lysine and proline and on the formation of collagen intermolecular cross-links were studied by using rat bone, cartilage and skin tissues. Dichloromethanediphosphonate decreased bone collagen solubility both in acetic acid and after pepsin treatment. Although none of the diphosphonates had any effect on the hydroxylation of proline, dichloromethane-diphosphonate, but not 1-hydroxyethane-1,1-diphosphonate, increased the number of hydroxylysine residues in the alpha-chains of bone, skin and cartilage collagen. The stimulatory effect was dose-dependent. The dichloromethanediphosphonate-mediated increase in hydroxylysine residues in bone and cartilage was manifested in an increase of dihydroxylysinonorleucine, the cross-link that is formed by the condensation of two hydroxylysine residues. The cross-link hydroxylysinonorleucine, a condensation product of hydroxylysine and lysine, on the other hand, was decreased. The total number of intermolecular cross-links was not changed by the diphosphonate.
利用大鼠的骨、软骨和皮肤组织,研究了二氯甲烷二膦酸盐和1-羟基乙烷-1,1-二膦酸盐对胶原蛋白溶解性、赖氨酸和脯氨酸羟化作用以及对胶原蛋白分子间交联形成的体内效应。二氯甲烷二膦酸盐降低了骨胶原蛋白在乙酸中和经胃蛋白酶处理后的溶解性。尽管两种二膦酸盐对脯氨酸的羟化作用均无影响,但二氯甲烷二膦酸盐而非1-羟基乙烷-1,1-二膦酸盐增加了骨、皮肤和软骨胶原蛋白α链中羟赖氨酸残基的数量。这种刺激作用呈剂量依赖性。二氯甲烷二膦酸盐介导的骨和软骨中羟赖氨酸残基的增加表现为二羟基赖氨酰正亮氨酸增加,二羟基赖氨酰正亮氨酸是由两个羟赖氨酸残基缩合形成的交联。另一方面,由羟赖氨酸和赖氨酸缩合形成的交联羟赖氨酰正亮氨酸减少。二膦酸盐并未改变分子间交联的总数。