|Galvin, Rachelle - LILLY, INDIANAPOLIS, IN|
Submitted to: Veterinary Pathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: November 6, 1996
Publication Date: N/A
Interpretive Summary: Atrophic rhinitis, a respiratory disease of pigs, is of major concern to the swine industry. There is an important need for new and better techniques to aid in the prevention and control of the disease. The disease has a complicated etiology involving the interaction of two bacterial agents, Bordetella bronchiseptica and Pasteurella multocida. The principal manifestation is deviation and shortening of the snout which results from altered remodeling of bone of the nasal passages. Systemic effects of atrophic rhinitis result in poor weight gains. Alone and together, these conditions adversely affect marketability of finished pigs and result in significant financial losses to producers. The effects on bone are due to a toxin produced by Pasteurella multocida and can be experimentally reproduced in pigs. Although these effects can be reproduced in pigs, a laboratory system for evaluating the mechanisms involved in bone remodeling was required. In this research, methods were developed to grow pig bone cells in culture; two types of cells were cultured, bone forming cells and bone resorbing cells. Examination of the effects of toxin on these cells showed that it interfered with normal processes by decreasing activities of bone forming cells and stimulating activities of bone resorbing cells. The development of this model system was critical to understanding the biochemical mechanisms of bone alteration involved in producing atrophic rhinitis. The findings of this research will benefit the swine industry by providing a means to evaluate different strategies for intervention in the pathogenesis of the disease, ultimately resulting in loss reduction and improved marketability of pigs.
Technical Abstract: The effect of Pasteurella multocida toxin (PMT) on porcine osteoclast and osteoblast differentiation was studied using in vitro cell culture systems. When grown in the presence of Vitamin D3, isolated porcine bone marrow cells formed multinucleated cells with features characteristic of osteoclasts. Exposure of bone marrow cells to Vitamin D3 and PMT during growth resulted in formation of increased numbers and earlier appearance o osteoclasts compared to controls. Ultra-filtered medium from PMT-treated cells likewise increased osteoclast numbers, suggesting that a soluble mediator may be involved in the action of PMT. When cell cultures were treated with fluorescein-labeled PMT, fluorescence was found within the cytoplasm of small, round cells that did not resemble either osteoclasts or osteoclastic precursor cells. Cultures of porcine bone marrow cells exposed to dexamethasone, ascorbic acid, and beta-glycerophosphate developed into osteoblastic cells that formed multilayered, mineralized nodules. Exposure of osteoblastic cultures to low concentrations of PMT resulted in retarded cell growth, formation of decreased numbers of nodules, and minimal to no mineralization in the nodules; higher concentrations of PMT resulted in increased cellular debris and poor growth of cells, with no nodule formation. These findings suggest that PMT may induce turbinate atrophy in pigs by increasing osteoclast numbers and inhibiting osteoblastic bone formation. The effect of PMT on osteoclastic differentiation and growth may not be due to direct effect on pre- osteoclastic cells, but rather due to alterations in the soluble mediator secretion by marrow stromal cells.