title: Calcitonin and prednisolone display antagonistic actions on bone and have synergistic effects in experimental arthritis.
abstract: We tested here the hypothesis that calcitonin and glucocorticoids, known to modulate bone metabolism, could have opposite actions on bone cells regulating expression of cytokine receptor activator of nuclear factor-kappaBeta ligand (RANKL) and osteoprotegerin (OPG). In the U2OS osteosarcoma cell line, calcitonin (10(-11) to 10(-9) mol/L) reduced RANKL and augmented OPG both at the mRNA and protein levels. Cell incubation with prednisolone (10(-8) to 10(-6) mol/L), the glucocorticoid chosen for this study, produced opposite results. These molecular studies prompted more functional analyses whereby osteoclast bone resorptive activity was determined. Calcitonin (10(-10) mol/L) abrogated the stimulating effect of 10 ng/ml RANKL or 10(-9) mol/L prednisolone; similar results were obtained with OPG. Assessment of calcitonin and prednisolone effects in an in vivo model of rheumatoid arthritis revealed partially surprising results. In fact, calcitonin not only preserved bone morphology (as assessed on day 18) in rats subjected to arthritis and treated with prednisolone (0.8 to 4 mg/kg daily from day 13) but also synergized with the steroid to elicit its antiarthritic effects. These results suggest that calcitonin could be used as a novel cotreatment to augment efficacy and reduce side effects associated with the prolonged use of steroids.
authors.affiliation: The William Harvey Research Institute, London, UK.
authors.forename: Lucia
authors.initials: L
authors.lastname: Mancini
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Paul-Clark
authors.forename: Guglielmo
authors.initials: G
authors.lastname: Rosignoli
authors.forename: Robert
authors.initials: R
authors.lastname: Hannon
authors.forename: Jo E
authors.initials: JE
authors.lastname: Martin
authors.forename: Ian
authors.initials: I
authors.lastname: Macintyre
authors.forename: Mauro
authors.initials: M
authors.lastname: Perretti
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000473:pathology; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D001862:Bone Resorption / Q000473:pathology; D001842:Bone and Bones / Q000187:drug effects* / Q000473:pathology; D002116:Calcitonin / Q000494:pharmacology*; D002460:Cell Line; D004357:Drug Synergism; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D008297:Male; D010010:Osteoclasts / Q000187:drug effects; D053244:Osteoprotegerin / Q000187:drug effects / Q000378:metabolism; D011239:Prednisolone / Q000494:pharmacology*; D053245:RANK Ligand / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D050071:Bone Density Conservation Agents; D005938:Glucocorticoids; D053244:Osteoprotegerin; D053245:RANK Ligand; D002116:Calcitonin; D011239:Prednisolone