Factors present in skin appear to enhance bone resorption in chronic otitis media. These skin factors were replicated in a series of experiments using an animal model. The presence of activated ...granulation tissue is a universal finding in bone resorption in otitis media. Skin promotes bone resorbing connective tissue by the action of keratin as a foreign body, by the enhancement of middle ear sepsis, by stimulation and activation of inflammatory cells and most importantly through the creation of pressure.
Collagenase was identified within naturally occurring rat chronic otitis media by the use of an immunohistochemical technique with peroxidase-antiperoxidase to stain the paraffin. Collagenase was ...found in fibroblasts, mononuclear cells, and osteoclast cells in the bone-resorbing area. Collagenase was found only in fibroblasts in contact with epithelial basal cells. Macrophages from rat peritoneum were cultured with different concentrations of a lipopolysaccharide. The prostaglandin E2 level reached a maximum during the 12- to 24-hour period in the presence of endotoxin. This prostaglandin E2 was confirmed by immunofluorescent staining. The endotoxin-activated macrophage produced an insignificant amount of collagenase. These findings suggest that activated macrophages may be able to stimulate fibroblast collagenase production through the chemical mediator prostaglandin E2. Also, the interaction between fibroblasts and epidermal cells appears to encourage and enhance the biochemical events resulting in bone resorption in chronic otitis media.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Keratin debris is a constant feature in middle-ear cholesteatoma. Keratin prepared from rat skin induced a foreign-body granuloma in the subcutaneous space in the rat. In vitro this granuloma ...produced high levels of bone-resorbing factors: prostaglandin E2, osteoclast-activating factor, and leucine aminopeptidase. In the in vivo study, keratin-induced granuloma in the rat middle ear caused partial resorption of the cochlear wall. Macrophages, fibroblasts, and osteoclastlike cells were found at bone-resorption areas. These cells appeared to be responsible for bone resorption through production of prostaglandin E2, osteoclast-activating factor, and proteases.
Laminaria, a hygroscopic seaweed material, was capable of absorbing fluid, and gradually swelled up to four times its diameter within 24 hours. Laminaria was used to induce pressure within the rat ...tympanic cavity. Resorption of bulla and cochlear walls occurred in all animals within two weeks. Preswelled laminaria inserted in the same area induced minimal bone resorption after two and three weeks. We also studied the effect of indomethacin, a specific inhibitor of prostaglandin synthesis, on bone resorption induced by physical force. In animals given indomethacine following insertion of laminaria, both granulation tissue formation and bone resorption were inhibited. Acid phosphatase activity appeared localized in the inflammatory granulation tissue in the bone resorption area, especially in osteoclasts, mononuclear cells and fibroblasts. Results of this study suggested that pressure created by laminaria caused bone resorption by stimulating osteoclasts and granulation tissue through biochemichal events. Pressure did not cause bone resorption directly.
Since collagen comprises over 90% of bone protein, collagenase appears to be a major factor in the resorption process of the organic matrix of bone. We have studied the mechanism of production of ...collagenase in cell cultures of rat skin fibroblasts and macrophages under various conditions. Production of collagenase by fibroblasts increased significantly with the addition of the conditioned medium obtained from the culture of endotoxin-activated rat peritoneal macrophages. This study concludes that the endotoxin-activated macrophages produced factor or factors which stimulate fibroblasts to produce collagenase.
