Overexpression of the human interleukin 1a gene causes osteopenia in mice.

ABSTRACT

OBJECTIVE: Osteoporosis is a major complication of chronic inflammatory diseases such as rheumatoid arthritis (RA). We describe disordered bone metabolism in transgenic mice that overexpress human interleukin 1a (hIL-1a). METHODS: Bone mineral density (BMD), microcomputed tomography (microCT), histomorphometry, and blood biochemical data of hIL-1a transgenic mice and littermate wild-type mice were examined. RESULTS: The femoral BMD of transgenic mice was decreased by 27.7% compared with wild-type mice. microCT revealed a marked reduction in the trabecular bone, and cortical thinning with an enlarged cavity was observed in femora of transgenic mice. Histomorphometric analysis revealed inhibition of several measures of bone formation, while the serum alkaline phosphatase level was reduced in transgenic mice; however, their indices of bone resorption were not elevated. CONCLUSION: Overexpression of hIL-1a causes osteopenia in mice. It was suggested that the systemic osteopenia in these transgenic mice occurred primarily as a result of decreased bone formation, with a reduction of bone mineralization rather than increased osteoclastic bone resorption. This may be one aspect of bone metabolism in RA that results in disease complications.