title: Calcitonin (but not calcitonin gene-related peptide) increases mouse bone cell proliferation in a dose-dependent manner, and increases mouse bone formation, alone and in combination with fluoride.
abstract: Previous in vitro studies have shown that salmon calcitonin had direct effects to increase parameters associated with embryonic chicken bone formation and to increase mouse and chicken osteoblast-line cell proliferation. The current studies demonstrate increased cell proliferation (i.e., [3H]-thymidine incorporation into DNA and tetrazolium salt reduction/deposition) in the osteoblastic murine cell line MC-3T3-E1 in response to salmon calcitonin (P less than 0.005) and to human calcitonin (P less than 0.005), but not to human calcitonin gene-related peptide. The current studies also show that salmon calcitonin increased several indices of murine bone formation. We found that 72 hours of exposure to salmon calcitonin [at 5 mU/ml-about 0.37 nM; mU/ml = milliunits of calcitonin activity/ml incubation medium (at 4,000 U/mg protein)] increased net 45Ca deposition (121% of control, P less than 0.05), net [3H]-proline incorporation 149% of control, P less than 0.001), and alkaline phosphatase activity (146% of control, P less than 0.01), in neonatal mouse half-calvaria. The calcitonin-dependent increase in alkaline phosphatase activity was not affected by co-incubation with 1 nM parathyroid hormone. Co-incubation with fluoride (which also increased net [3H]-proline incorporation and alkaline phosphatase activity in neonatal mouse half-calvaria, P less than 0.05, for each) enhanced the osteogenic response to low-dose calcitonin, (i.e., co-incubation with fluoride shifted the biphasic calcitonin dose-response curve to a range of lower calcitonin concentrations). The calcitonin-fluoride combinations had proportional effects on net [3H]-proline incorporation and alkaline phosphatase in the treated mouse calvaria (r = 0.78, P less than 0.005).
authors.affiliation: Department of Medicine, Loma Linda University, California.
authors.forename: J R
authors.initials: JR
authors.lastname: Farley
authors.forename: S L
authors.initials: SL
authors.lastname: Hall
authors.forename: N M
authors.initials: NM
authors.lastname: Tarbaux
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001842:Bone and Bones / Q000378:metabolism; D002116:Calcitonin / Q000494:pharmacology*; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D005459:Fluorides / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D010012:Osteogenesis / Q000187:drug effects*; D012474:Salmon
chemical_list: D002116:Calcitonin; D000469:Alkaline Phosphatase; D015740:Calcitonin Gene-Related Peptide; D005459:Fluorides; D002118:Calcium