ECTS2016 Poster Presentations Steroid hormones and receptors (3 abstracts)
Phosphorylation of S122 in ERα is important for the skeletal response to estrogen treatment
Karin Gustafsson 1 , Helen Farman 1 , Vikte Lionikaite 1 , Jianyao Wu 1 , Petra Henning 1 , Annica Andersson 1 , Ulrika Islander 1 , Angelina Bernardi 1 , Sara Windahl 1 , Sofia Skrtic 1 , Klara Sjögren 1 , Antti Koskela 3 , Juha Tuukkanen 3 , Andree Krust 2 , Pierre Chambon 2 , Claes Ohlsson 1 & Marie Lagerquist 1
1Centre for Bone and Arthritis Research, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden; 2Department of Functional Genomics, IGBMC, Collège de France, Illkirch, France; 3Unit of Cancer Research and Translational Medicine, MRC Oulu and Department of Anatomy and Cell Biology, University of Oulu, Oulu, Finland.
It is well established that estrogen, mainly via estrogen receptor alpha (ERα), has positive effects on bone, but estrogen is not considered as a treatment option against osteoporosis due to negative side-effects in other tissues. ERα is widely subjected to posttranslational modifications (PTMs), which can affect cellular responses to estrogen in a tissue specific manner by influencing the function of ERα and its interactions with other proteins. The in vivo role of PTMs of ERα for the skeleton is unknown but the PTM site S122 in ERα is known to modulate ERα transcriptional activity in vitro. Our aim was to investigate if phosphorylation of the PTM site S122 in ERα is involved in ERα-mediated bone effects in vivo. To this end, we used mice with a point mutation in S122 (S122A) and compared them to WT littermates. Twelve-week-old mice were ovariectomized and treated with estradiol (E2, 160 ng/day per mouse) or vehicle for four weeks. Tibiae were analyzed using μCT and humeri were exposed to a three-point bending test. E2 treatment increased cortical thickness in both WT and S122A females, however, the cortical thickness in E2-treated S122A mice was significantly decreased compared to E2-treated WT mice (−6%, P<0.05). Importantly, the functional three-point bending test demonstrated that E2 treatment increased maximal load at failure (Fmax) in WT mice (+25% P<0.001) while no significant effect of E2 treatment was observed in S122A mice, demonstrating that phosphorylation of S122 is crucial for the E2 effect on mechanical strength of cortical bone. In conclusion, our results show that the S122 phosphorylation site is involved in the skeletal response to estrogen treatment and this finding is the first in vivo proof of a physiological role of phosphorylation in ERα.
Volume 5
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Bone Abstracts
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