Inhibition of sympathetic tone via hypothalamic descending pathway propagates glucocorticoid-induced endothelial impairment and osteonecrosis of the femoral head.

ABSTRACT: Osteonecrosis of the femoral head (ONFH) is a common complication of glucocorticoid (GC) therapy. Recent advances demonstrate that sympathetic nerves regulate bone homeostasis, and GCs lower the sympathetic tone. Here, we show that the dramatically decreased sympathetic tone is closely associated with the pathogenesis of GC-induced ONFH. GCs activate the glucocorticoid receptor (GR) but hinder the activation of the mineralocorticoid receptor (MR) on neurons in the hypothalamic paraventricular nucleus (PVN). This disrupts the balance of corticosteroid receptors (GR/MR) and subsequently reduces the sympathetic outflow in the PVN. Vascular endothelial cells rapidly react to inhibition of sympathetic tone by provoking endothelial apoptosis in adult male mice treated with methylprednisolone (MP

SUBMITTER: Shao W 

PROVIDER: S-EPMC11549335 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature