The glucocorticoid receptor in osteoprogenitors regulates bone mass and marrow fat

The Journal of Endocrinology
Jessica L PierceMeghan E McGee-Lawrence

Abstract

Excess fat within bone marrow is associated with lower bone density. Metabolic stressors such as chronic caloric restriction (CR) can exacerbate marrow adiposity, and increased glucocorticoid signaling and adrenergic signaling are implicated in this phenotype. The current study tested the role of glucocorticoid signaling in CR-induced stress by conditionally deleting the glucocorticoid receptor (GR) in bone marrow osteoprogenitors (Osx1-Cre) of mice subjected to CR and ad libitum diets. Conditional knockout of the GR (GR-CKO) reduced cortical and trabecular bone mass as compared to wildtype (WT) mice under both ad libitum and CR conditions. No interaction was detected between genotype and diet, suggesting that the GR is not required for CR-induced skeletal changes. The lower bone mass in GR-CKO mice, and the further suppression of bone by CR, resulted from suppressed bone formation. Interestingly, treatment with the -adrenergic receptor antagonist propranolol mildly but selectively improved metrics of cortical bone mass in GR-CKO mice during CR, suggesting interaction between adrenergic and glucocorticoid signaling pathways that affects cortical bone. GR-CKO mice dramatically increased marrow fat under both ad libitum and CR-f...Continue Reading

Citations

Aug 3, 2021·Frontiers in Endocrinology·Erica L SchellerBeata Lecka-Czernik
Nov 9, 2021·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Jessica L PierceMeghan E McGee-Lawrence

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