Alterations in osteoclast morphology following long-term 17beta-estradiol administration in the mouse
1 Department of Orthopaedic Surgery, Carolinas Medical Center, Charlotte, N.C., USA
2 Laboratory of Molecular Pathology, Department of Pathology and Immunology Graduate Program, University of Texas Southwestern Medical Center, Dallas, TX., USA
3 Department of Pathology, University of Chicago, 5841 S. Maryland Ave., Room BH S-329, Chicago, IL., USA
4 Department of Comparative Medicine, Oklahoma Medical Research Foundation, Oklahoma City, OK., USA
BMC Cell Biology 2001, 2:3 doi:10.1186/1471-2121-2-3Published: 20 February 2001
Although the role of the osteoclast in bone resorption is becoming better understood, much remains to be learned about osteoclastogenesis and the exact mechanism of action of anti-resorbing agents such as 17β-estradiol. This study investigated bone and morphologic osteoclast alterations following long-term estrogen administration to the B6D2F1 mouse. B6D2F1 mice aged 4-5 weeks were exposed to high levels of estrogen via implanted silastic tubing for at least 12 weeks; controls received empty tubing. Femurs of control and treated mice were assessed with radiology, quantitative histomorphometry and transmission electron microscopy.
After 8 weeks of treatment, there was radiologic evidence of severe osteosclerosis and 86% of femoral marrow space was replaced with bone. After 12 weeks histologic studies of treated animals revealed that osteoclasts were positive for tartrate-resistant acid phosphatase but showed markedly abnormal ultrastructure which prevented successful bone resorption.
Findings extend our understanding of osteoclast structure and function in the mouse exposed in vivo to high doses of estrogen. Ultrastructural examination showed that osteoclasts from estrogen-treated mice were unable to seal against the bone surface and were unable to form ruffled borders.