The influence of 1-hydroxyethane-1,1-diphosphonate and dichloromethanediphosphonate on lysine hydroxylation and cross-link formation in rat bone, cartilage and skin collagen.
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.
D000818:Animals; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism; D004002:Clodronic Acid / Q000494:pharmacology*; D003094:Collagen / Q000096:biosynthesis*; D004164:Diphosphonates / Q000494:pharmacology*; D012968:Etidronic Acid / Q000494:pharmacology*; D006900:Hydroxylation; D008239:Lysine / Q000378:metabolism*; D051381:Rats; D012867:Skin / Q000187:drug effects / Q000378:metabolism
D004164:Diphosphonates; D004002:Clodronic Acid; D003094:Collagen; D008239:Lysine; D012968:Etidronic Acid