Mineralisation of collagen rich soft tissues and osteocyte lacunae in Enpp1(-/-) mice.
Mineralisation of collagen rich soft tissues and osteocyte lacunae in Enpp1(-/-) mice.
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DOI：
10.1016/j.bone.2014.09.016
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发表时间：
2014-12
期刊：
影响因子：
4.1
通讯作者：
Orriss, Isabel R.
中科院分区：
文献类型：
--
作者：
Hajjawi, Mark O. R.;MacRae, Vicky E.;Huesa, Carmen;Boyde, Alan;Millan, Jose Luis;Arnett, Timothy R.;Orriss, Isabel R.
外核苷酸焦磷酸酶/磷酸二酯酶（NPP）将核苷酸三磷酸水解为相应的核苷酸单磷酸和矿化抑制剂焦磷酸（PPi）。这项研究使用缺乏NPP 1的小鼠模型（Enpp 1 −/−）检查了NPP 1在骨细胞，破骨细胞和皮质骨中的作用。我们使用微计算机断层扫描（μCT）来研究NPP 1缺失如何影响皮质骨结构;在0.9 μm下扫描8、15和22周龄小鼠的肱骨。尽管8周龄Enpp 1 −/−小鼠的皮质骨没有明显变化，但在老年动物中观察到了显著差异。在22周的Enpp 1 −/−小鼠中，皮质骨体积减少了28%，而皮质孔隙率在15周和22周分别减少了30%和60%。这是伴随着高达15%的封闭孔径减少和55%的孔的数量减少。在15周和22周的Enpp 1 −/−动物中，皮质厚度减少了35%，骨内膜直径增加了23%。因此，Enpp 1 −/−小鼠的皮质骨更薄，孔隙更少，骨髓空间更大。扫描电子显微镜（SEM）显示皮质骨中血管通道的大小和数量减少，骨细胞陷窝的平均平面面积减少40%。我们注意到，从Enpp 1 −/−小鼠的长骨中分离的活骨细胞数量减少≤ 50%。相反，破骨细胞的形成和吸收活性不受NPP 1缺失的影响。对Enpp 1 −/−小鼠的μCT和组织学分析也显示了关节和椎骨以及软组织（包括须囊、耳廓和气管）的钙化。这种钙化随着动物年龄的增长而恶化。总之，这些数据突出了NPP 1在调节软组织和骨骼组织钙化中的关键作用。我们研究了NPP 1在骨细胞、破骨细胞和皮质骨中的作用。NPP 1基因敲除小鼠骨细胞陷窝的大小和数量减少。在NPP 1敲除小鼠中硬化蛋白水平增加。破骨细胞的形成和再吸收活性不受NPP 1缺失的影响。缺乏NPP 1的小鼠显示富含胶原的软组织广泛钙化。
Ecto-nucleotide pyrophosphatase/phosphodiesterases (NPPs) hydrolyse nucleotide triphosphates to the corresponding nucleotide monophosphates and the mineralisation inhibitor, pyrophosphate (PPi). This study examined the role of NPP1 in osteocytes, osteoclasts and cortical bone, using a mouse model lacking NPP1 (Enpp1−/−). We used microcomputed tomography (μCT) to investigate how NPP1 deletion affects cortical bone structure; excised humerus bones from 8, 15 and 22-week old mice were scanned at 0.9 μm. Although no changes were evident in the cortical bone of 8-week old Enpp1−/− mice, significant differences were observed in older animals. Cortical bone volume was decreased 28% in 22-week Enpp1−/− mice, whilst cortical porosity was reduced 30% and 60% at 15 and 22-weeks, respectively. This was accompanied by up to a 15% decrease in closed pore diameter and a 55% reduction in the number of pores. Cortical thickness was reduced up to 35% in 15 and 22-week Enpp1−/− animals and the endosteal diameter was increased up to 23%. Thus, the cortical bone from Enpp1−/− mice was thinner and less porous, with a larger marrow space. Scanning electron microscopy (SEM) revealed a decrease in the size and number of blood vessel channels in the cortical bone as well as a 40% reduction in the mean plan area of osteocyte lacunae. We noted that the number of viable osteocytes isolated from the long bones of Enpp1−/− mice was decreased ≤ 50%. In contrast, osteoclast formation and resorptive activity were unaffected by NPP1 deletion. μCT and histological analysis of Enpp1−/− mice also revealed calcification of the joints and vertebrae as well as soft tissues including the whisker follicles, ear pinna and trachea. This calcification worsened as the animals aged. Together, these data highlight the key role of NPP1 in regulating calcification of both soft and skeletal tissues. We examine the role of NPP1 in osteocytes, osteoclasts and cortical bone. Osteocyte lacunae are reduced in size and number in NPP1 knockout mice. Sclerostin levels are increased in NPP1 knockout mice. Osteoclast formation and resorptive activity are unaffected by NPP1 deletion. Mice lacking NPP1 display widespread calcification of collagen rich soft tissues.
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影响因子：
6
作者：
Anderson, HC;Harmey, D;Millán, JL
通讯作者：
Millán, JL
影响因子：
6.2
作者：
Johnson, K;Goding, J;Terkeltaub, R
通讯作者：
Terkeltaub, R
DOI：
10.1073/pnas.142063399
发表时间：
2002-07-09
影响因子：
11.1
作者：
Hessle, L;Johnson, KA;Millán, JL
通讯作者：
Millán, JL
影响因子：
6.2
作者：
Lin, Chuwen;Jiang, Xuan;He, Lin
通讯作者：
He, Lin
影响因子：
4.8
作者：
ARNETT, TR;DEMPSTER, DW
通讯作者：
DEMPSTER, DW