The effects of 1-hydroxyethane-1,1-diphosphonate and dichloromethanediphosphonate on collagen synthesis by rabbit articular chondrocytes and rat bone cells

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Abstract
Effects of dichloromethanediphosphonate on the synthesis of collagen were assessed in isolated rabbit articular chondrocytes, isolated rat calvaria bone cells and bone explants from rats treated with the diphosphonates. Dichloromethanediphosphonate but not 1-hydroxyethane-1,1-diphosphonate causes articular chondrocytes to increase net collagen biosynthesis when measured as 3H-labeled or as non-radioactive material in a dose-related fashion. The increment in collagen synthesis was still evident with cells that were exposed continuously to the diphosphonate in primary and secondary culture; it declined with cells in tertiary culture and was absent after the 4th subculture. The type of collagen was not affected by the diphosphonate. The synthesis of collagen by bone cells was increased with dichloromethanediphosphonate. No effects were detected when 1-hydroxyethane-1,1-diphosphonate was tested. When calvaria and tibias from diphosphonate-treated rats were cultured in vitro, the positive effect of dichloromethanediphosphonate on collagen synthesis was evident. 1-Hydroxyethane-1,1-diphosphonate decreased the incorporation of [3H]proline into the collagen of calvaria and osseous tibial shafts and showed no effect on the collagen synthesis of the cartilaginous tibial heads.