β-Adrenergic Blockade and Leptin Replacement Effectively Mitigate Disuse Bone Loss
β-Adrenergic Blockade and Leptin Replacement Effectively Mitigate Disuse Bone Loss
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DOI：
10.1359/jbmr.081241
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发表时间：
2009-05-01
影响因子：
6.2
通讯作者：
Bloomfield, Susan A.
中科院分区：
文献类型：
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作者：
Baek, Kyunghwa;Bloomfield, Susan A.
我们的目的是测试β-肾上腺素能阻滞对后肢去负荷（HU）诱导的骨丢失和血清瘦素的影响，并将这些反应与瘦素替代观察到的反应进行比较。将成年雄性大鼠随机分为6组（每组n = 10）：在28天HU期间用溶媒（VEHHU）、瘦素类似物（LEPHU）或β-受体阻滞剂（BBHU）处理的HU大鼠和用相同的三种药物处理并成对饲喂HU大鼠的笼活动对照（CC）。在第0天和第28天，进行胫骨近端的pQCT扫描和血清采集用于瘦素测定，并评估胫骨近端松质骨的组织形态计量学测量。在VEHHU组中观察到的松质骨vBMD降低20%，在BBHU大鼠和LEPHU大鼠中减半。BBHU大鼠的骨形成率（BFR）得以保持，但LEPHU大鼠的骨形成率未保持。BB和LEP治疗可消除HU引起的吸收表面增加3倍。在BBHU和LEPHU大鼠中，28天HU后血清瘦素的降低减弱，并且可预测HU后BFR的降低。在HU期间通过外周给予β受体阻滞剂阻断交感肾上腺素能信号传导，通过刺激成骨细胞活性和抑制骨细胞活性减轻废用诱导的松质骨骨量减少。β-肾上腺素能阻滞剂在HU期间对骨细胞的直接作用可能通过减轻循环瘦素减少的间接作用而增强，这可能是通过解除对脂肪细胞释放瘦素的抑制。
Our objective was to test effects of beta-adrenergic blockade on hindlimb unloading (HU)-induced bone loss and serum leptin and to compare these responses with those observed with leptin replacement. Adult male rats were randomized into six groups (n = 10 each): HU rats treated with vehicle (VEHHU), leptin analog (LEPHU), or beta-blocker (BBHU) during a 28-day HU and cage activity controls (CC) treated with the same three agents and pair-fed to HU rats. On days 0 and 28, pQCT scans of proximal tibia and serum collections for leptin assays were performed, and histomorphometric measures of proximal tibia cancellous bone were assessed. The 20% decrease in cancellous vBMD observed in the VEHHU group was halved in BBHU rats and LEPHU rats. Bone formation rate (BFR) in BBHU rats, but not in LEPHU rats, was preserved. The 3-fold increase in resorption surface with HU was abolished by BB and LEP treatments. The decrease in serum leptin after a 28-day HU was attenuated in BBHU and LEPHU rats and was predictive of the decrease in BFR with HU. Blocking sympathetic adrenergic signaling by peripheral administration of a beta-blocker during HU mitigates disuse-induced decreases in cancellous bone mass through stimulation of osteoblastic activity and suppression of osteoclastic activity. A direct effect of beta-adrenergic blockade on bone cells during HU may be enhanced by an indirect effect mitigating reductions in circulating leptin, possibly through disinhibition of leptin release from adipocytes.