Propranolol and parathyroid hormone synergistically improve bone volume fraction by suppressing resorption

Autor: Treyball, Annika, Bergeron, Audrey C., Brooks, Daniel J., Nevola, Kathleen T., Hashmi, Hina, Nagano, Kenichi, Barlow, Deborah, Houseknecht, Karen L., Baron, Roland, Bouxsein, Mary L., Guntur, Anyonya R., Motyl, Katherine J.
Jazyk: angličtina
Rok vydání: 2020
Předmět:
DOI: 10.1101/2020.01.08.898320
Popis: Although the non-selective β-blocker, propranolol, improves bone density with PTH treatment in mice, the mechanism of this effect is unclear. To address this, we used a combination of in vitro and in vivo approaches to address how propranolol influences bone remodeling in the context of PTH treatment. In vitro , propranolol amplified the acute, PTH-induced, intracellular calcium signal and elevated Igf1 expression in osteoblasts. In vivo , intermittent PTH and propranolol had synergistic effects in the trabecular bone of the distal femur. The most striking finding was a complete suppression of PTH-induced bone resorption. Despite this, PTH-induced receptor activator of nuclear factor kappa-B ligand (RANKL) mRNA and protein levels were unaltered by propranolol. Interestingly, propranolol suppressed differentiation of primary osteoclasts, suggesting a novel direct influence of propranolol on osteoclasts in vivo . Taken together, this work suggests combining propranolol with PTH could be beneficial to patients with extremely low bone density.
Databáze: OpenAIRE