Regulation of skeletal remodeling by the endocannabinoid system
Regulation of skeletal remodeling by the endocannabinoid system
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DOI：
10.1196/annals.1402.014
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发表时间：
2007-01-01
期刊：
影响因子：
--
通讯作者：
Bab, Itai A.
中科院分区：
文献类型：
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作者：
Bab, Itai A.
自从内源性大麻素系统被发现以来，其在少数生物系统中的存在和参与已有报道。最近，骨架已被确定为一个主要的内源性大麻素靶标，通过神经元CB1和主要是外周CB2大麻素受体。CB1存在于骨骼的交感神经末梢，而CB2表达于成骨细胞和破骨细胞，这两种细胞分别是骨形成细胞和骨吸收细胞。此外，骨架似乎是受CB2生理调节的主要系统。CB2基因缺陷的小鼠表现出与年龄相关的明显加速的骨丢失，而女性的CB2基因座与低骨密度和骨质疏松性骨折有关。由于CB2的激活通过抑制骨吸收和刺激骨形成来减轻实验诱导的骨丢失，而且合成的大麻素是稳定的和口服的，因此基于合成的CB2激动剂的治疗是抗骨质疏松药物开发的一个有前景的新靶点。
Since the discovery of the endocannabinoid system, its presence and involvement have been reported in a handful of biological systems. Recently, the skeleton has been identified as a major endocannabinoid target through both the neuronal CB1 and predominantly peripheral CB2 cannabinoid receptors. CB1 is present in sympathetic nerve terminals in bone, whereas CB2 is expressed in osteoblasts and osteoclasts, the respective bone-forming and -resorbing cells. Furthermore, the skeleton appears as the main system physiologically regulated by CB2. CB2-deficient mice show a markedly accelerated age-related bone loss and the CB2 locus in women is associated with low bone density and osteoporotic fractures. Since activation of CB2 attenuates experimentally induced bone loss by inhibiting bone resorption and stimulating bone formation, and because synthetic cannabinoids are stable and orally available, a therapy based on synthetic CB2 agonists is a promising novel target for antiosteoporotic drug development.