Systemic administration of low-dose naltrexone increases bone mass due to blockade of opioid growth factor receptor signaling in mice osteoblasts.
Systemic administration of low-dose naltrexone increases bone mass due to blockade of opioid growth factor receptor signaling in mice osteoblasts.
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由于阻断小鼠成骨细胞中的阿片生长因子受体信号传导，全身给予低剂量纳曲酮可增加骨量。
DOI：
10.1016/j.lfs.2019.03.069
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发表时间：
2019
期刊：
影响因子：
6.1
通讯作者：
Togari A.
中科院分区：
文献类型：
--
作者：
Tanaka K;Kondo H;Hamamura K;Togari A.
阿片受体阻滞剂如纳洛酮和纳洛酮被认为具有增加骨量的作用。然而，起作用的机制尚未澄清。我们研究了纳洛酮对成骨细胞的影响，并测定了成骨细胞中阿片生长因子受体（OGFR）的表达。纳洛酮阻断OGFR和其他典型阿片受体。因此，我们设计了实验来阐明纳曲酮对骨组织的影响，通过检查成骨细胞中OGFR信号传导的生理作用和纳曲酮全身给药后小鼠骨结构的变化。我们在OGFR激动剂甲硫氨酸脑啡肽（met-enk）的存在下培养MC 3 T3-E1细胞。然后，我们测量细胞增殖活性并分析细胞增殖相关基因的表达水平。对于我们的体内实验，我们每天给小鼠腹腔注射纳洛酮，持续28天，并给对照组动物等量的生理盐水。处死小鼠后，我们进行了显微计算机断层扫描和骨形态分析。此外，低剂量纳曲酮管理显着增加他们的股骨骨量，骨形成率，成骨细胞数量/骨表面值时，比较相同的变量在control group.SignificanceOur结果表明，纳曲酮增加骨量由于成骨细胞数量增量引起的OGFR信号块。阿片受体阻滞剂与阿片拮抗剂一样具有作为骨质疏松症治疗药物的潜力。
AimsOpioid receptor blockers such as naloxone and naltrexone have been suggested to have a bone mass-increasing effect. However, the mechanisms at play have not been clarified. We examined the effects of naltrexone on osteoblasts and determined the expression of opioid growth factor receptor (OGFR) in osteoblasts. Naltrexone blocks the OGFR and other canonical opioid receptors. Thus, we designed experiments to clarify the effects of naltrexone on bone tissue by examining the physiological role of OGFR signaling in osteoblasts and the changes in bone structure after naltrexone systemic administration in mice.Main methodsWe used mouse osteoblast-like cell line MC3T3-E1 forin vitroexperiments. We cultured MC3T3-E1 cells in the presence of the OGFR agonist met-enkephalin (met-enk). Then, we measured cell proliferation activity and analyzed the expression levels of cell proliferation-related genes. For ourin vivoexperiments, we administered naltrexone intraperitoneally to mice daily for 28 days and administered the animals in the control group equivalent volumes of saline. After sacrificing the mice, we performed micro-computed tomography and bone morphology analyses.Key findingsMet-enk suppressed cell proliferation in MC3T3-E1 cells. Moreover, Low dose naltrexone administration significantly increased their femoral bone mass, bone formation ratio, and osteoblast number/bone surface values when comparing the values for the same variables in the control group.SignificanceOur results suggest that naltrexone increases bone mass due to osteoblast number increments caused by the OGFR signaling block. Opioid receptor blockers have potential as therapeutic agents for osteoporosis as well as opioid antagonists.
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影响因子：
5
作者：
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2000-12
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影响因子：
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作者：
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DOI：
--
发表时间：
1989
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Taiwo,YO;Basbaum,AI;Perry,F;Levine,JD
通讯作者：
Levine,JD