Estrogen directly down-regulates the bone-resorbing activity of mature osteoclasts through nuclear estrogen receptor α

The decrease in estrogen level that follows the onset ofmenopause causes rapid bone loss, resulting in osteoporosis.However, the mechanism remains unclear, especially concerningthe regulation of bone-resorbing osteoclasts. Here we analyzedthe function of estrogen and its receptor in matureosteoclasts. We found that estrogen directly inhibitedbone-resorption by purified rabbit mature-osteoclasts.Moreover, using a RT-PCR technique, we report that nuclearestrogen receptor (ER) α but not ERβ is expressed in mature osteoclasts. The antisense oligodeoxynucleotide for ERα inhibited the reductionin osteoclastic bone-resorbing activity caused by estrogen. We conclude that in part estrogen directly inhibits the bone-resorbing activity of mature osteoclasts through the ERα.