Prevention of bone loss by modulation of estrogen signaling

Fractures caused by bone loss are associated with suffering and increased mortality in patients and great costs for society. It is well established that estrogen protects the skeleton and prevents bone loss. However, the use of this hormone as a therapeutic drug against bone loss is restricted due to adverse effects.

Estrogen signaling is regulated in a tissue-specific manner.

I therefore hypothesize that targeting of specific estrogen signaling pathways will result in tissue-specific therapeutic agents which can protect against bone loss without giving rise to adverse effects.My recent pivotal findings that i) a substantial part of the bone-protective effect of estrogen is mediated via estrogen receptor alpha (ERα) situated in the cell membrane, and ii) that estrogen signaling in neuronal cells affects bone mass, will be explored in experimental studies during a five-year period.

I have recently developed an advanced unique transgenic mouse model which allows both cell-type specific and temporal studies of membrane-initiated ERα signaling and to study neuronal estrogen signaling I will use novel transgenic mouse models and a chemogenetic approach.The overall aim of this project proposal is to characterize membrane-initiated and neuronal ERα signaling, two novel cutting-edge research areas, in order to facilitate the development of new tissue-specific treatments against bone loss which avoid adverse effects.