The anabolic action of intermittent parathyroid hormone on cortical bone depends partly on its ability to induce nitric oxide-mediated vasorelaxation in BALB/c mice

Cell Biochemistry and Function
S GohinM Marenzana

Abstract

There is strong evidence that vasodilatory nitric oxide (NO) donors have anabolic effects on bone in humans. Parathyroid hormone (PTH), the only osteoanabolic drug currently approved, is also a vasodilator. We investigated whether the NO synthase inhibitor L-NAME might alter the effect of PTH on bone by blocking its vasodilatory effect. BALB/c mice received 28 daily injections of PTH[1-34] (80 µg/kg/day) or L-NAME (30 mg/kg/day), alone or in combination. Hindlimb blood perfusion was measured by laser Doppler imaging. Bone architecture, turnover and mechanical properties in the femur were analysed respectively by micro-CT, histomorphometry and three-point bending. PTH increased hindlimb blood flow by >30% within 10 min of injection (P < 0.001). Co-treatment with L-NAME blocked the action of PTH on blood flow, whereas L-NAME alone had no effect. PTH treatment increased femoral cortical bone volume and formation rate by 20% and 110%, respectively (P < 0.001). PTH had no effect on trabecular bone volume in the femoral metaphysis although trabecular thickness and number were increased and decreased by 25%, respectively. Co-treatment with L-NAME restricted the PTH-stimulated increase in cortical bone formation but had no clear-cut ef...Continue Reading

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Citations

Aug 18, 2017·The Journal of Endocrinology·Rhonda D Prisby
Apr 24, 2017·Diabetologia·Beata Lecka-Czernik
Dec 17, 2020·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Chenggui ZhangChunli Song
Jul 6, 2021·Biochemical Pharmacology·Tianhong ChenJingfeng Li

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Methods Mentioned

BETA
confocal microscopy

Software Mentioned

Ct
GraphPad
Skyscan
Matlab
Osteometrics
Image J
Prism
NRecon
An

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