Bisphosphonates and bone resorption: effects on collagenase and lysosomal enzyme excretion.
When added to cultures of parathyroid hormone (PTH)-stimulated bones, dichloromethylenebisphosphonate (C12MBP) and 3-amino-1-hydroxypropydilene-1,1-bisphosphonate (AHPrBP) inhibit completely and in a parallel manner the development of resorption lacunae, the loss of calcium by the explants and their PTH-induced excretion of lysosomal hydrolases (beta-glucuronidase and N-acetyl-beta-glucosaminidase). The loss of collagen (hydroxyproline) by the bones is usually less inhibited than their loss of calcium and their heparin-induced excretion of collagenase is unaffected. To interpret these data, it is proposed that these bisphosphonates act more on the activity of osteoclasts, suppressing simultaneously their excretion of lysosomal enzymes and their erosion of mineralized bone matrix, than on that of other cell types (osteoblasts ?) responsible for collagenase production and the removal of uncalcified collagen.
D000118:Acetylglucosaminidase / Q000378:metabolism; D000818:Animals; D001862:Bone Resorption / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D004002:Clodronic Acid / Q000494:pharmacology*; D003864:Depression, Chemical; D004164:Diphosphonates / Q000494:pharmacology*; D005966:Glucuronidase / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology; D008247:Lysosomes / Q000201:enzymology; D051379:Mice; D003012:Microbial Collagenase / Q000378:metabolism; D009924:Organ Culture Techniques; D010006:Osteoblasts / Q000201:enzymology; D010010:Osteoclasts / Q000187:drug effects / Q000201:enzymology; D000077268:Pamidronate; D010281:Parathyroid Hormone / Q000494:pharmacology
D004164:Diphosphonates; D010281:Parathyroid Hormone; D004002:Clodronic Acid; D006493:Heparin; D005966:Glucuronidase; D000118:Acetylglucosaminidase; D003012:Microbial Collagenase; D000077268:Pamidronate; D002118:Calcium