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


CONCLUSIONS
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.
Aoki
Yoshihiro
Y
Department of Orthopaedic Surgery, National Defense Medical College, Tokorozawa, Saitama, Japan. grd501@gr.ndmc.ac.jp
Ichimura
Shoichi
S
Kikuchi
Toshiyuki
T
Yoshihara
Yasuo
Y
Kogawa
Masakazu
M
Tada
Norihiro
N
Nemoto
Koichi
K
Fujikawa
Kyosuke
K
D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D015519:Bone Density / Q000235:genetics; D001851:Bone Diseases, Metabolic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000097:blood; D004195:Disease Models, Animal; D005269:Femur / Q000000981:diagnostic imaging / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D014057:Tomography, X-Ray Computed
D007375:Interleukin-1; D000469:Alkaline Phosphatase; D002118:Calcium