Long-term growth retardation occurs in children and osteopenias occur among children and adults who have been burned or suffer from other injuries that result in a systemic inflammatory response. Currently, the specific mechanisms that bring about these changes are currently not known. It is therefore the aim of this proposal to learn the specific organ, tissue, and cellular skeletal events that occur following a thermal injury and to correlate these changes to alterations in inflammatory cytokines and adrenal glucocorticoids. These goals will be achieved utilizing a thermal injury mouse model and analysis tools such as histomorphometry, cellular density, cell formation rate, apoptosis, and cytokine and adrenal glucocorticoid levels. Additionally, since tumor necrosis factor alpha has been shown to alter bone formation, osteoblast and chondrocyte apoptosis, and endochondral ossification in other inflammatory conditions, a tumor necrosis factor-alpha receptor deficient knockout mouse will be utilized to learn its specific role(s) in bone loss from a thermal injury. By learning the mechanisms that lead to skeletal changes in systemic inflammatory conditions it is hoped that long-term therapeutic strategies can be developed to mitigate these detrimental skeletal alterations. ? ?
