MAMMALIAN MATURE OSTEOCLASTS AS ESTROGEN TARGET-CELLS

The decrease in estrogen levels that follows the onset of menopause ca uses rapid bone loss, resulting in osteoporosis. However, the mechanis m by which this occurs remains unclear, especially concerning the regu lation of osteoclasts, i.e. the bone-resorbing cells. Using a pit assa y involving isolated mature osteoclasts from rabbit long bones, we fou nd that estrogen inhibited the bone-resorbing activity in a dose- and time-dependent manner. Furthermore, we clarified by Northern analysis that estrogen down-regulated the mRNA levels of cathepsin K/OC-2 and t hat putative estrogen receptor (ER) mRNA was expressed in these osteoc lasts. Moreover, other sizes of mRNAs that hybridized with ER cDNA pro be were found in these cells. Our results suggest that osteoclasts may be indeed target cells for estrogen and that estrogen might regulate a part of bone metabolism through osteoclasts. (C) 1996 Academic Press , Inc.