Intermittent PTH 1-34 administration improves the marrow microenvironment and endothelium-dependent vasodilation in bone arteries of aged rats

摘要

Inflammation coincides with diminished marrow function, vasodilation of blood vessels, and bone mass. Intermittent parathyroid hormone (PTH) administration independently improves marrow and vascular function, potentially impacting bone accrual. Currently, the influence of marrow and intermittent PTH administration on aged bone blood vessels has not been examined. Vasodilation of the femoral principal nutrient artery (PNA) was assessed in the presence and absence of marrow. Furthermore. we determined the influence of PTH 1-34 on 1) endothclium-dependent vasodilation and signaling pathways [i.e., nitric oxide (NO) and prostacyclin (PGI(2))], 2) endothelium-independent vasodilation, 3) cytokine production by marrow cells, and 4) bone microarchitecture and bone static and dynamic properties. Young (4-6 mo) and old (22-24 mo) male Fischer-344 rats were treated with PTH 1-34 or a vehicle for 2 wk. In the absence and presence of marrow, femoral PNAs were given cumulative doses of acetylcholine, with and without the NO and PGI(2) blockers, and dielhylamine NONOate. Marrow-derived cytokines and bone parameters in the distal femur were assessed. Exposure to marrow diminished endothelium-dependent vasodilation in young rats. Reduced bone volume and NO-mediated vasodilation occurred with old age and were partially reversed with PTH. Additionally, PTH treatment in old rats restored endothelium-dependent vasodilation in the presence of marrow and augmented IL-10, an anti-inflammatory cytokine. Endothelium-independent vasodilation was unaltered, and PTH treatment reduced osteoid surfaces in old rats. In conclusion, the marrow microenvironment reduced vascular function in young rats, and PTH treatment improved the marrow microenvironment and vasodilation with age.