Effect of Pasteurella multocida toxin on bone resorption in vitro

Félix, R.; Fleisch, H.; Frandsen, P. L.

doi:10.1128/iai.60.12.4984-4988.1992

Cited by 40 publications

(15 citation statements)

References 32 publications

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“…Thus this protein is as active a mediator of bone resorption as the most potent osteolytic cytokine, IL-1 (116,125). PMT-induced bone resorption was completely inhibited by calcitonin, a circulating hormone able to inhibit osteoclast function, and inhibitors of cyclo-oxygenase partially inhibited this bone resorption (17). While Pasteurella multocida infections in pigs are associated only with nasal turbinate atrophy, it appears from this and in vivo data that PMT can act on bones other than the nasal bones.…”

Section: Fig 3 the Possible Points Of Interaction Between Osteolytimentioning

confidence: 75%

“…These bones have a different embryonic derivation and often respond differently to the same osteolytic mediator (e.g., TNF or epidermal growth factor, etc.). However, in both assays, PMT produced maximal bone resorption at the extremely low concentration of 5 ng/ml (approximately 30 pM [17]). We have shown that recombinant PMT stimulates significant murine calvarial bone resorption at concentrations as low as 0.1 ng/ml (Ͻ1 pM [76b]).…”

Section: Fig 3 the Possible Points Of Interaction Between Osteolytimentioning

confidence: 94%

“…A surprising finding was that intraperitoneal injection of PMT resulted in increased osteoclast density and bone loss both in the maxillofacial skeleton and in the appendicular skeleton of rats (73). The activity of PMT has been tested in the two major in vitro bone resorption assays-the murine calvarial assay and the murine long bone assay (17). These bones have a different embryonic derivation and often respond differently to the same osteolytic mediator (e.g., TNF or epidermal growth factor, etc.).…”

Section: Fig 3 the Possible Points Of Interaction Between Osteolytimentioning

confidence: 99%

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Bacterially induced bone destruction: mechanisms and misconceptions

et al. 1996

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Normal bone remodelling requires the coordinated regulation of the genesis and activity of osteoblast and osteoclast lineages. Any interference with these integrated cellular systems can result in dysregulation of remodelling with the consequent loss of bone matrix. Bacteria are important causes of bone pathology in common conditions such as periodontitis, dental cysts, bacterial arthritis, and osteomyelitis. It is now established that many of the bacteria implicated in bone diseases contain or produce molecules with potent effects on bone cells. Some of these molecules, such as components of the gram-positive cell walls (lipoteichoic acids), are weak stimulators of bone resorption in vitro, while others (PMT, cpn60) are as active as the most active mammalian osteolytic factors such as cytokines like IL-1 and TNF. The complexity of the integration of bone cell lineage development means that there are still question marks over the mechanism of action of many well-known bone-modulatory molecules such as parathyroid hormone. The key questions which must be asked of the now-recognized bacterial bone-modulatory molecules are as follows: (i) what cell population do they bind to, (ii) what is the nature of the receptor and postreceptor events, and (iii) is their action direct or dependent on the induction of secondary extracellular bone-modulating factors such as cytokines, eicosanoids, etc. In the case of LPS, this ubiquitous gram-negative polymer probably binds to osteoblasts or other cells in bone through the CD14 receptor and stimulates them to release cytokines and eicosanoids which then induce the recruitment and activation of osteoclasts. This explains the inhibitor effects of nonsteroidal and anticytokine agents on LPS-induced bone resorption. However, other bacterial factors such as the potent toxin PMT may act by blocking the normal maturation pathway of the osteoblast lineage, thus inducing dysregulation in the tightly regulated process of resorption and replacement of bone matrix. At the present time, it is not possible to define a general mechanism by which bacteria promote loss of bone matrix. Many bacteria are capable of stimulating bone matrix loss, and the information available would suggest that each organism possesses different factors which interact with bone in different ways. With the rapid increase in antibiotic resistance, particularly with Staphylococcus aureus and M. tuberculosis, organisms responsible for much bone pathology in developed countries only two generations ago, we would urge that much greater attention should be focused on the problem of bacterially induced bone remodelling in order to define pathogenetic mechanisms which could be therapeutic targets for the development of new treatment modalities.

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Section: Fig 3 the Possible Points Of Interaction Between Osteolytimentioning

confidence: 75%

Section: Fig 3 the Possible Points Of Interaction Between Osteolytimentioning

confidence: 94%

Section: Fig 3 the Possible Points Of Interaction Between Osteolytimentioning

confidence: 99%

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Bacterially induced bone destruction: mechanisms and misconceptions

et al. 1996

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“…Calvarium culture. Culture conditions similar to those described previously (7) were used. Briefly, calvarium explants from 4-to 5-day-old ddy mice, bred in our breeding facilities, were obtained aseptically.…”

Section: Methodsmentioning

confidence: 99%

Effect of MALP-2, a Lipopeptide from Mycoplasma fermentans , on Bone Resorption In Vitro

et al. 1999

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Mycoplasmas may be associated with rheumatoid arthritis in various animal hosts. In humans, mycoplasma arthritis has been recorded in association with hypogammaglobulinemia. Mycoplasma fermentans is one mycoplasma species considered to be involved in causing arthritis. To clarify which mycoplasmal compounds contribute to the inflammatory, bone-destructive processes in arthritis, we used a well-defined lipopeptide, 2-kDa macrophage-activating lipopeptide (MALP-2) from M. fermentans, as an example of a class of macrophageactivating compounds ubiquitous in mycoplasmas, to study its effects on bone resorption. MALP-2 stimulated osteoclast-mediated bone resorption in murine calvaria cultures, with a maximal effect at around 2 nM. Antiinflammatory drugs inhibited MALP-2-mediated bone resorption by about 30%. This finding suggests that MALP-2 stimulates bone resorption partially by stimulating the formation of prostaglandins. Since interleukin-6 (IL-6) stimulates bone resorption, we investigated IL-6 production in cultured calvaria. MALP-2 stimulated the liberation of IL-6, while no tumor necrosis factor was detectable. Additionally, MALP-2 stimulated low levels of NO in calvaria cultures, an effect which was strongly increased in the presence of gamma interferon, causing an inhibition of bone resorption. MALP-2 stimulated the bone-resorbing activity of osteoclasts isolated from long bones of newborn rats and cultured on dentine slices without affecting their number. In bone marrow cultures, MALP-2 inhibited the formation of osteoclasts. It appears that MALP-2 has two opposing effects: it increases the bone resorption in bone tissue by stimulation of mature osteoclasts but inhibits the formation of new ones.

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“…PGE2 increases cartilage growth by stimulating chondrocyte proliferation and bone resorption by stimulating osteoclast proliferation (O'Keefe et al, 1992). Evidence for direct cytokine action on bone consists of a Pasteurella multocida induced bone resorption in vitro (Felix et al, 1992) and…”

Section: Bone Growth and Resorptionmentioning

confidence: 99%

Impact of immune system activation on the rate, efficiency, and composition of growth, the efficiency of nutrient utilization and lysine needs of growing pigs

Williams

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Service (NAHMS) had sows which tested positive for Transmissible Gastroenteritis and 51.5% of the herds had sows which tested positive for Swine Influenza Virus (National Swine Survey, 1992). However, management technologies are increasingly being employed that reduce or minimize the exposure of pigs to antigens. These technologies include all inall out pig flow, multiple-site production, medicated early weaning, and depopulationrepopulation procedures. Consequently, the degree of exposure to antigens and the associated levels of immune system activation differ substantially among herds or groups of pigs. The impact of level of immune system activation on tissue growth and nutrient utilization and thus nutrient requirements in pigs is not known. Therefore, it was the objective of this dissertation research to evaluate the impact of level of immune system activation on the rate, efficiency, and composition of body growth, the utilization of nutrients for these processes, and dietary lysine required for these processes in pigs fed from 6 to 114 kg. Dissertation Organization The dissertation is divided into a literamre review, two papers, and a General Summary. The papers were prepared in a style appropriate for submission to the Journal of Animal Science. N.H. Williams is the senior author on both papers.

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Effect of Pasteurella multocida toxin on bone resorption in vitro

Cited by 40 publications

References 32 publications

Bacterially induced bone destruction: mechanisms and misconceptions

Bacterially induced bone destruction: mechanisms and misconceptions

Effect of MALP-2, a Lipopeptide from Mycoplasma fermentans , on Bone Resorption In Vitro

Impact of immune system activation on the rate, efficiency, and composition of growth, the efficiency of nutrient utilization and lysine needs of growing pigs

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