Although the nonselective β-blocker, propranolol, improves bone density with parathyroid hormone (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 female C57BL/6J mice, intermittent PTH and propranolol administration had complementary effects in the trabecular bone of the distal femur and fifth lumbar vertebra (L 5 ), with combination treatment achieving microarchitectural parameters beyond that of PTH alone. Combined treatment improved the serum bone formation marker, procollagen type 1 N propeptide (P1NP), but did not impact other histomorphometric parameters relating to osteoblast function at the L 5 . In vitro, propranolol amplified the acute, PTH-induced, intracellular calcium signal in osteoblast-like cells. The most striking finding, however, was suppression of PTH-induced bone resorption. Despite this, PTH-induced receptor activator of nuclear factor κ-B ligand (RANKL) mRNA and protein levels were unaltered by propranolol, which led us to hypothesize that propranolol could act directly on osteoclasts. Using in situ methods, we found Adrb2 expression in osteoclasts in vivo, suggesting β-blockers may directly impact osteoclasts. Consistent with this, we found propranolol directly suppresses osteoclast differentiation in vitro. Taken together, this work suggests a strong anti-osteoclastic effect of nonselective β-blockers in vivo, indicating that combining propranolol with PTH could be beneficial to patients with extremely low bone density.
43Although the non-selective β-blocker, propranolol, improves bone density with PTH treatment in 44 mice, the mechanism of this effect is unclear. To address this, we used a combination of in vitro 45 and in vivo approaches to address how propranolol influences bone remodeling in the context of 46 PTH treatment. In vitro, propranolol amplified the acute, PTH-induced, intracellular calcium 47 signal and elevated Igf1 expression in osteoblasts. In vivo, intermittent PTH and propranolol had 48 synergistic effects in the trabecular bone of the distal femur. The most striking finding was a 49 complete suppression of PTH-induced bone resorption. Despite this, PTH-induced receptor 50 activator of nuclear factor kappa-B ligand (RANKL) mRNA and protein levels were unaltered 51 by propranolol. Interestingly, propranolol suppressed differentiation of primary osteoclasts, 52 suggesting a novel direct influence of propranolol on osteoclasts in vivo. Taken together, this 53 work suggests combining propranolol with PTH could be beneficial to patients with extremely 54 low bone density. 55 56 57The sympathetic nervous system (SNS) plays a critical role in the regulation of bone remodeling. 58
Congenital melanocytic nevi arise from overgrowth or disrupted migration of melanocyte precursor in the neural crest. They are also known as coat-sleeve, stocking, bathing trunk or garment nevi. The colour ranges from brown to black, with the lesions presenting as flat to raised nevi. Lesions presenting at birth with a diameter greater than 20cm are labelled giant congenital melanocytic nevi. Risk increases with an increase in the number of satellite lesions near the giant nevus. Management includes regular clinical follow-up monitoring of changes in the lesion and surgical procedures in cases with risk of melanoma and psychological support. The purpose of this case presentation is to describe a rare issue of giant congenital melanocytic nevi in a newborn, along with a literature review and discussion on possible management options.
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