POTENTIATION OF OSTEOCLAST BONE-RESORPTION ACTIVITY BY INHIBITION OF NITRIC-OXIDE SYNTHASE
POTENTIATION OF OSTEOCLAST BONE-RESORPTION ACTIVITY BY INHIBITION OF NITRIC-OXIDE SYNTHASE
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DOI：
10.1073/pnas.91.9.3569
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发表时间：
1994-04-26
影响因子：
11.1
通讯作者：
NICKOLS, GA
中科院分区：
文献类型：
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作者：
KASTEN, TP;COLLINOSDOBY, P;NICKOLS, GA
我们在体外研究了调节一氧化氮(NO)水平对破骨细胞介导的骨吸收的影响，以及一氧化氮合酶(NOS)抑制剂对体内骨密度的影响。以黄递酶为基础的组织化学染色的骨切片或高度浓缩的破骨细胞培养的NOS活性表明，破骨细胞具有大量的NOS活性，这可能是基础NO产生的原因。鸡破骨细胞在牛骨切片上培养36小时，分别加入或不加入NO生成剂硝普钠或一氧化氮合酶抑制剂N-硝基-L-精氨酸甲酯和氨基胍。与对照组相比，硝普钠能显著减少骨陷窝的数量和平均陷窝面积。而N-硝基-L-精氨酸甲酯或氨基胍对一氧化氮合酶的抑制作用则显著增加骨陷窝的数目和平均每窝吸收面积。在骨质疏松症模型中，氨基胍加剧了去卵巢大鼠的骨密度丢失。氨基胍还导致假手术大鼠的骨密度下降。体外和体内抑制一氧化氮合酶活性可明显增强破骨细胞活性。这些发现表明，破骨细胞培养中内源性NO的产生可能调节吸收活动。骨微环境中细胞对NOS和NO水平的调节可能是破骨细胞骨吸收局部控制的敏感机制。
We have examined the effects of modulating nitric oxide (NO) levels on osteoclast-mediated bone resorption in vitro and the effects of nitric oxide synthase (NOS) inhibitors on bone mineral density in vivo. Diaphorase-based histochemical staining for NOS activity of bone sections or highly enriched osteoclast cultures suggested that osteoclasts exhibit substantial NOS activity that may account for basal NO production. Chicken osteoclasts were cultured for 36 hr on bovine bone slices in the presence or absence of the NO-generating agent sodium nitroprusside or the NOS inhibitors N-nitro-L-arginine methyl ester and aminoguanidine. Nitro-prusside markedly decreased the number of bone pits and the average pit area in comparison with control cultures. On the other hand, NOS inhibition by N-nitro-L-arginine methyl ester or aminoguanidine dramatically increased the number of bone pits and the average resorption area per pit. In a model of osteoporosis, aminoguanidine potentiated the loss of bone mineral density in ovariectomized rats. Aminoguanidine also caused a loss of bone mineral density in the sham-operated rats. Inhibition of NOS activity in vitro and in vivo resulted in an apparent potentiation of osteoclast activity. These findings suggest that endogenous NO production in osteoclast cultures may regulate resorption activity. The modualtion of NOS and NO levels by cells within the bone microenvironment may be a sensitive mechanism for local control of osteoclast bone resorption.