Endocannabinoids and the regulation of bone metabolism
Endocannabinoids and the regulation of bone metabolism
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DOI：
10.1111/j.1365-2826.2008.01675.x
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发表时间：
2008-05-01
影响因子：
3.2
通讯作者：
Zimmer, A.
中科院分区：
文献类型：
--
作者：
Bab, I.;Ofek, O.;Zimmer, A.
在包括人类在内的哺乳动物中，骨代谢表现为一个持续的建模/重塑过程，其中骨矿化基质不断更新。最近，内源性大麻素系统的主要成分已在骨骼中报道。成骨细胞，成骨细胞和其他成骨细胞系的细胞，以及破骨细胞，骨吸收细胞及其前体，合成内源性大麻素和2-花生四烯醇甘油（2-AG）。CB1大麻素受体存在于靠近成骨细胞的交感神经末梢。骨2-AG水平升高激活这些CB1受体，传递脑-骨信号，创伤性脑损伤诱导的骨形成刺激就是例证。在这个过程中，逆行的CB1信号抑制去甲肾上腺素的释放，减轻骨形成的强直性交感抑制。CB2受体通过成骨细胞和破骨细胞表达。它们的激活刺激骨形成并抑制骨吸收。缺乏cb2的小鼠表现出明显加速的与年龄相关的骨质流失。卵巢切除术引起的骨质流失可以通过CB2特异性激动剂来预防和挽救。因此，合成稳定且可口服的CB2配体为开发新型抗骨质疏松治疗方法提供了基础。女性的CNR2基因（编码CB2）与低骨密度有关，为识别女性患骨质疏松症的风险提供了一种检测方法。
In mammals, including humans, bone metabolism is manifested as an ongoing modelling/remodelling process whereby the bone mineralised matrix is being continuously renewed. Recently, the main components of the endocannabinoid system have been reported in the skeleton. Osteoblasts, the bone forming cells, and other cells of the osteoblastic lineage, as well as osteoclasts, the bone resorbing cells, and their precursors, synthesise the endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG). CB1 cannabinoid receptors are present in sympathetic nerve terminals in close proximity to osteoblasts. Activation of these CB1 receptors by elevated bone 2-AG levels communicates brain-to-bone signals as exemplified by traumatic brain injury-induced stimulation of bone formation. In this process, the retrograde CB1 signalling inhibits noradernaline release and alleviates the tonic sympathetic restrain of bone formation. CB2 receptors are expressed by osteoblasts and osteoclasts. Their activation stimulates bone formation and suppresses bone resorption. CB2-deficient mice display a markedly accelerated age-related bone loss. Ovariectomy-induced bone loss can be both prevented and rescued by a CB2 specific agonist. Hence, synthetic CB2 ligands, which are stable and orally available, provide a basis for developing novel anti-osteoporotic therapies, free of psychotropic effects. The CNR2 gene (encoding CB2) in women is associated with low bone mineral density, offering an assay for identifying females at risk of developing osteoporosis.