We seek to elucidate the mechanisms of bone resorption in otospongiosis. Bone resorption in the otic capsules of an animal model will be induced mainly by immunization with type II collagen, the principal type collagen in cartilage. The resulting otospongiotic lesion will be measured by morphometric study using a computerized videoplan image analysis system to study: a) the extend of bone resorption by measuring total volume of bone resorption from serial sections, b) total volume of otosclerotic bone formation, c) bone resorbing activities (levels of collagenase, cyclooxygenase, and acid phosphatase) and bone forming activity (alkaline phosphatase) histochemically or immunohistochemically with an intigrating microscpoic photometer attached to the videoplan image analysis system. Sodium fluoride, immunosuppressors (imuran, prednison), and anti-prostaglandin systhetase (indomethacin) will be given to animals to determine if these agents will inhibit bone resorption. Progesterone will be given to the animals to determine if this hormone will promote an earlier occurrence or greater extent of otospongiosis in response to type II collagen. Effects of anti-type II collagen antibody on macrophages, fibroblasts and bone cells will be studied. These cells will be studied either separately or combined to determine if any morphological changes and biochemical functions including secretion of bone resorbing activities in the present of anti-type II collagen antibody. In vitro studies will help us understand mechanisms of pathogenesis of otospongiotic lesion in the cellular and biochemical levels and supports our in vivo studies.
