Propranolol Promotes Bone Formation and Limits Resorption Through Novel Mechanisms During Anabolic Parathyroid Hormone Treatment in Female C57BL/6J Mice.
Propranolol Promotes Bone Formation and Limits Resorption Through Novel Mechanisms During Anabolic Parathyroid Hormone Treatment in Female C57BL/6J Mice.
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DOI：
10.1002/jbmr.4523
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发表时间：
2022-05
影响因子：
6.2
通讯作者：
Motyl, Katherine J.
中科院分区：
文献类型：
--
作者：
Treyball, Annika;Bergeron, Audrey C.;Brooks, Daniel J.;Langlais, Audrie L.;Hashmi, Hina;Nagano, Kenichi;Barlow, Deborah;Neilson, Ryan J.;Roy, Tyler A.;Nevola, Kathleen T.;Houseknecht, Karen L.;Baron, Roland;Bouxsein, Mary L.;Guntur, Anyonya R.;Motyl, Katherine J.
关键词：
尽管非选择性β受体阻滞剂普萘洛尔可改善PTH治疗小鼠的骨密度，但这种作用的机制尚不清楚。为了解决这个问题，我们使用了体外和体内方法的组合，以解决普萘洛尔如何影响骨重建的背景下，PTH治疗。在雌性C57 BL/6 J小鼠中，间歇性PTH和普萘洛尔给药在股骨远端和L5椎骨的骨小梁中具有互补作用，联合给药获得的微结构参数超过单独PTH。联合治疗改善了血清骨形成标志物P1 NP，但不影响与L5成骨细胞功能相关的其他组织形态学参数。在体外，普萘洛尔放大急性，PTH诱导，在成骨细胞样细胞的细胞内钙信号。然而，最引人注目的发现是抑制PTH诱导的骨吸收。尽管如此，PTH诱导的核因子κ-B配体受体激活剂（RANKL）mRNA和蛋白水平未被普萘洛尔改变，这使我们假设普萘洛尔可以直接作用于破骨细胞。采用原位方法，我们发现Adrb 2在体内破骨细胞中表达，表明β受体阻滞剂可能直接影响破骨细胞。与此相一致，我们发现普萘洛尔直接抑制破骨细胞的分化在体外。总之，这项工作表明，非选择性β受体阻滞剂在体内具有很强的抗骨质疏松作用，表明普萘洛尔与PTH联合治疗可能对骨密度极低的患者有益。
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 female C57BL/6J mice, intermittent PTH and propranolol administration had complementary effects in the trabecular bone of the distal femur and L5 vertebra, with combination treatment achieving micro-architectural parameters beyond that of PTH alone. Combined treatment improved the serum bone formation marker, P1NP, but did not impact other histomorphometric parameters relating to osteoblast function at the L5. 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 kappa-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 non-selective β-blockers in vivo, indicating that combining propranolol with PTH could be beneficial to patients with extremely low bone density.
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影响因子：
4.1
作者：
Pierroz, Dominique D.;Bouxsein, Mary L.;Ferrari, Serge L.
通讯作者：
Ferrari, Serge L.
影响因子：
3.6
作者：
Baker, JG;Hall, IP;Hill, SJ
通讯作者：
Hill, SJ
多巴胺信号传导在雌性小鼠中非典型抗精神病药物利投资利培酮中骨丢失的发病机理中的一种新作用。
影响因子：
4.1
作者：
Motyl KJ;Beauchemin M;Barlow D;Le PT;Nagano K;Treyball A;Contractor A;Baron R;Rosen CJ;Houseknecht KL
通讯作者：
Houseknecht KL
DOI：
10.1084/jem.20102608
发表时间：
2011-04-11
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kajimura D;Hinoi E;Ferron M;Kode A;Riley KJ;Zhou B;Guo XE;Karsenty G
通讯作者：
Karsenty G
影响因子：
6.2
作者：
DeMambro, Victoria E.;Maile, Laura;Wai, Christine;Kawai, Masanobu;Cascella, Teresa;Rosen, Clifford J.;Clemmons, David
通讯作者：
Clemmons, David