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Down‐regulation of miR‐21 biogenesis by estrogen action contributes to osteoclastic apoptosis
Author(s) -
Sugatani Toshifumi,
Hruska Keith A.
Publication year - 2013
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.24471
Subject(s) - estrogen , autocrine signalling , fas ligand , apoptosis , microbiology and biotechnology , biogenesis , biology , cancer research , medicine , endocrinology , chemistry , programmed cell death , cell culture , gene , biochemistry , genetics
Estrogen inhibits osteoclastogenesis and induces osteoclastic apoptosis; however, the molecular mechanisms remain controversial. Recently, a group has demonstrated that osteoclasts are a direct target for estrogen because estrogen stimulates transcription of the Fas Ligand (FasL) gene in osteoclasts, which in turn causes cell death through an autocrine mechanism. In contrast, other groups have shown that the cells are an indirect target for estrogen because estrogen fails to stimulate the transcription of that in osteoclasts. Thus, two quite different molecular mechanisms have been suggested to explain the effects of estrogen in osteoclastic apoptosis. Here we show that the proapoptotic effect of estrogen during osteoclastogenesis is regulated by a posttranscriptional increase in FasL production by down‐regulated microRNA‐21 (miR‐21) biogenesis. Previously, we reported that miR‐21 is highly expressed in osteoclastogenesis. We found that estrogen down‐regulates miR‐21 biogenesis so that FasL, the targets of miR‐21, protein levels are posttranscriptionally increased that induce osteoclastic apoptosis. Moreover, the gain‐of‐function of miR‐21 rescued the apoptosis. In addition, we failed to detect estrogen‐enhanced FasL levels at mRNA levels. Thus, osteoclastic survival is controlled by autocrine actions of FasL regulated by estrogen and miR‐21 plays a central role during estrogen‐controlled osteoclastogenesis. J. Cell. Biochem. 114: 1217–1222, 2013. © 2012 Wiley Periodicals, Inc.