title: Pasteurella multocida toxin stimulates bone resorption by osteoclasts via interaction with osteoblasts.
abstract: In this study we used an in vitro assay system with osteoblast and osteoclast co-cultures to assess the effect of purified recombinant Pasteurella multocida toxin on bone resorption. Resorption was measured by the release of a telopeptide breakdown product of type I collagen. It was found that P. multocida did not stimulate bone resorption by osteoclasts directly and also did not stimulate bone breakdown via the release of collagenase or other proteases from osteoblasts. During co-culture of osteoblasts and osteoclasts, with cell-cell contact prevented, P. multocida toxin produced no significant effect. Osteoblast-conditioned media gave a biphasic effect; low concentrations of P. multocida toxin stimulated bone resorption, whereas 100 ng/ml inhibited resorption by osteoclasts. However, when both cell types were co-cultured with cell-cell contact permitted, P. multocida toxin induced a large concentration-dependent increase in bone resorption over a 7-day period. This suggested that P. multocida toxin causes bone breakdown via an osteoblast-dependent mechanism and that a membrane-bound receptor may be involved.
authors.affiliation: Institute for Animal Health, Compton, Newbury, Berkshire, RG20 7NN, UK.
authors.forename: P B
authors.initials: PB
authors.lastname: Mullan
authors.forename: A J
authors.initials: AJ
authors.lastname: Lax
mesh_terms: D000818:Animals; D001426:Bacterial Proteins; D001427:Bacterial Toxins / Q000633:toxicity*; D001862:Bone Resorption / Q000209:etiology*; D002450:Cell Communication; D002478:Cells, Cultured; D002642:Chick Embryo; D003094:Collagen / Q000032:analysis; D024042:Collagen Type I; D003470:Culture Media / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D010006:Osteoblasts / Q000502:physiology*; D010010:Osteoclasts / Q000502:physiology*; D016979:Pasteurella multocida; D010455:Peptides / Q000032:analysis; D012886:Skull / Q000166:cytology
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D024042:Collagen Type I; D003470:Culture Media; C062258:Pasteurella multocida toxin; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D003094:Collagen