Downregulation of beta-catenin and transdifferentiation of human osteoblasts to adipocytes under estrogen deficiency.
OBJECTIVE
Postmenopausal osteoporosis, caused by estrogen deficiency, is characterized by the structural deterioration of bone accompanied by an increase in bone marrow adipocytes. Transgenic animal models have shown that there is a reciprocal relationship between osteoblastogenesis and adipogenesis in vivo. The present study investigated whether the estrogen and the canonical Wnt signaling pathways are linked together and regulate the phenotype and function, differentiation and proliferation of human osteoblasts using an in vitro estrogen-deficiency model.


METHODS
Human osteoblasts (hFOB 1.19) and fulvestrant, an estrogen receptor blocker, were used to mimic estrogen deficiency in vitro. Osteogenic and adipogenic differentiation was measured by using specific stains and microscopy, as well as by measuring the expression of bone cell-specific markers with reverse transcription polymerase chain reaction. Expression of estrogen receptor-alpha (ERalpha) and beta-catenin was detected in Western blots and by immunoprecipitation.


RESULTS
The cells expressed the 46-kDa and the 77-kDa ERalpha isoforms and beta-catenin. Fulvestrant reduced expression of ERalpha and beta-catenin. beta-Catenin was co-immunoprecipitated with ERalpha, indicating that these two proteins form a new signaling complex and transcription factor. In addition, it induced intracellular lipid droplet accumulation and downregulation of bone cell markers, indicating adipocyte differentiation.
Foo
Clara
C
School of Anatomy and Human Biology, The University of Western Australia, Perth, Australia.
Frey
Soenke
S
Yang
Hong Hyun
HH
Zellweger
Rene
R
Filgueira
Luis
L
D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D054338:Cell Transdifferentiation / Q000187:drug effects*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D047628:Estrogen Receptor alpha / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology*; D006801:Humans; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011485:Protein Binding; D015398:Signal Transduction / Q000187:drug effects; D051176:beta Catenin / Q000378:metabolism*
D047628:Estrogen Receptor alpha; D004967:Estrogens; D051176:beta Catenin