Sclerostin activity plays a key role in the negative effect of glucocorticoid signaling on osteoblast function in mice

Bone Research
Eric E BeierJ Edward Puzas

Abstract

Stress during prenatal development is correlated with detrimental cognitive and behavioral outcomes in offspring. However, the long-term impact of prenatal stress (PS) and disrupted glucocorticoid signaling on bone mass and strength is not understood. In contrast, the detrimental effect of lead (Pb) on skeletal health is well documented. As stress and Pb act on common biological targets via glucocorticoid signaling pathways and co-occur in the environment, this study first sought to assess the combined effect of stress and Pb on bone quality in association with alterations in glucocorticoid signaling. Bone parameters were evaluated using microCT, histomorphometry, and strength determination in 8-month-old male mouse offspring subjected to PS on gestational days 16 and 17, lifetime Pb exposure (100 p.p.m. Pb in drinking water), or to both. Pb reduced trabecular bone mass and, when combined with PS, Pb unmasked an exaggerated decrement in bone mass and tensile strength. Next, to characterize a mechanism of glucocorticoid effect on bone, prednisolone was implanted subcutaneously (controlled-release pellet, 5 mg·kg(-1) per day) in 5-month-old mice that decreased osteoblastic activity and increased sclerostin and leptin levels. Furt...Continue Reading

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Citations

Mar 29, 2018·Journal of Molecular Endocrinology·Yasmine HachemiJan Tuckermann
May 6, 2020·International Journal of Molecular Sciences·Annelies De MaréAnja Verhulst

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Methods Mentioned

BETA
atomic absorption spectroscopy
PCR
protein assay

Software Mentioned

Osteomeasure
Scanco

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