The serotonin 5-HT2B receptor controls bone mass via osteoblast recruitment and proliferation
The serotonin 5-HT2B receptor controls bone mass via osteoblast recruitment and proliferation
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DOI：
10.1096/fj.07-9209com
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发表时间：
2008-02-01
期刊：
影响因子：
4.8
通讯作者：
de Vernejoul, M. -C.
中科院分区：
文献类型：
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作者：
Collet, C.;Schiltz, C.;de Vernejoul, M. -C.
单胺5-羟色胺（5-HT）是一种众所周知的神经递质，在外周组织中也很重要。一些研究表明，5-HT参与骨代谢。从我们最初观察到在体外成骨细胞分化过程中5-HT 2B受体（5 HT（2B）R）表达增加开始，我们研究了5-HT 2BR基因敲除小鼠体内推定的骨表型。有趣的是，5-HT 2BR突变雌性小鼠显示骨密度降低，从4个月大开始显著，并在12和18个月时加剧。这种经组织形态计量学证实的骨质减少似乎是由于骨形成减少，因为1）在4至12月龄的5-HT 2BR突变小鼠中，骨髓前体的碱性磷酸酶阳性集落形成单位能力显著降低，2）来自突变小鼠的离体原代成骨细胞表现出增殖减少和分化延迟，和3）在5-HT 2BR耗尽（遗传或药理学失活产生）后，成骨细胞中的钙掺入显著减少。这些发现支持了这样的假设，即5-HT 2BR受体促进成骨细胞的募集和增殖，其缺乏导致骨质减少，这与年龄有关。我们在这里表明，第一次，5-HT 2BR受体是5-HT在骨形成的生理介质，并可能在老年妇女骨质疏松症的发病。
The monoamine serotonin (5-HT), a well-known neurotransmitter, is also important in peripheral tissues. Several studies have suggested that 5-HT is involved in bone metabolism. Starting from our original observation of increased 5-HT2B receptor (5HT(2B)R) expression during in vitro osteoblast differentiation, we investigated a putative bone phenotype in vivo in 5-HT2BR knockout mice. Of interest, 5-HT2BR mutant female mice displayed reduced bone density that was significant from age 4 months and had intensified by 12 and 18 months. This histomorphometrically confirmed osteopenia seems to be due to reduced bone formation because 1) the alkaline phosphatase-positive colony-forming unit capacity of bone marrow precursors was markedly reduced in the 5-HT2BR mutant mice from 4 to 12 months of age, 2) ex vivo primary osteoblasts from mutant mice exhibited reduced proliferation and delayed differentiation, and 3) calcium incorporation was markedly reduced in osteoblasts after 5-HT2BR depletion (produced genetically or by pharmacological inactivation). These findings support the hypothesis that the 5-HT2BR receptor facilitates osteoblast recruitment and proliferation and that its absence leads to osteopenia that worsens with age. We show here, for the first time, that the 5-HT2BR receptor is a physiological mediator of 5-HT in bone formation and, potentially, in the onset of osteoporosis in aging women.