Sclerostin is expressed in osteoclasts from aged mice and reduces osteoclast-mediated stimulation of mineralization.
Sclerostin is expressed in osteoclasts from aged mice and reduces osteoclast-mediated stimulation of mineralization.
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DOI：
10.1002/jcb.24537
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发表时间：
2013-08
影响因子：
4
通讯作者：
Oursler, Merry Jo
中科院分区：
文献类型：
--
作者：
Ota, Kuniaki;Quint, Patrick;Ruan, Ming;Pederson, Larry;Westendorf, Jennifer J.;Khosla, Sundeep;Oursler, Merry Jo
在成年早期，破骨细胞介导的骨吸收先于成骨细胞介导的骨形成，但在衰老过程中，骨形成无法跟上骨吸收的步伐。我们之前发现了破骨细胞产生的几种促进骨形成的因素。在这项研究中，我们确定破骨细胞产生的因子是否会导致衰老过程中骨形成受损。我们之前发现 18 至 22 个月之间的小鼠会出现与年龄相关的骨质流失。从 6 周、12 个月和 18 至 24 个月大的小鼠中分离出骨髓来源的前破骨细胞，并在体外分化为破骨细胞。收集条件培养基并比较成骨细胞矿化支持。来自各个年龄段的破骨细胞的条件培养基能够支持骨髓基质细胞的矿化。与基础培养基相比，浓缩 6 周龄和 12 个月龄小鼠骨髓细胞来源的破骨细胞的条件培养基增强了矿化支持，而来自 18 至 24 个月龄小鼠骨髓来源的破骨细胞的浓缩条件培养基抑制了矿化。这一观察结果表明，矿化抑制剂是由衰老的鼠破骨细胞分泌的。基因和蛋白质分析显示，与 6 周大的小鼠细胞相比，24 个月大的小鼠细胞的条件培养基中的 Wnt 拮抗剂硬化素显着升高。针对硬化蛋白的抗体中和了衰老小鼠细胞浓缩条件培养基对矿化的影响。硬化素主要由幼年动物的骨细胞产生。这项研究表明，老年小鼠的破骨细胞也会产生一定数量的硬化蛋白，这可能会导致与年龄相关的骨形成损伤。
Osteoclast-mediated bone resorption precedes osteoblast-mediated bone formation through early adulthood, but formation fails to keep pace with resorption during aging. We previously identified several factors produced by osteoclasts that promote bone formation. In this study, we determined if osteoclast-produced factors contribute to the impaired bone formation with aging. We previously found that mice between the ages of 18 and 22 months develop age-related bone loss. Bone marrow-derived pre-osteoclasts were isolated from 6-week, 12-month, and 18- to 24-month-old mice and differentiated into osteoclasts in vitro. Conditioned media were collected and compared for osteoblast mineralization support. Conditioned medium from osteoclasts from all ages was able to support mineralization of bone marrow stromal cells. Concentrating the conditioned medium from 6-week-old and 12-month-old mouse marrow cells-derived osteoclasts enhanced mineralization support whereas concentrated conditioned medium from 18- to 24-month-old mouse marrow-derived osteoclasts repressed mineralization compared to base medium. This observation suggests that an inhibitor of mineralization was secreted by aged murine osteoclasts. Gene and protein analysis revealed that the Wnt antagonist sclerostin was significantly elevated in the conditioned media from 24-month-old mouse cells compared to 6-week-old mouse cells. Antibodies directed to sclerostin neutralized the influences of the aged mouse cell concentrated conditioned media on mineralization. Sclerostin is primarily produced by osteocytes in young animals. This study demonstrates that osteoclasts from aged mice also produce sclerostin in quantities that may contribute to the age-related impairment in bone formation.
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影响因子：
4.2
作者：
RUBIN, CT;BAIN, SD;MCLEOD, KJ
通讯作者：
MCLEOD, KJ
影响因子：
6.2
作者：
Li, Xiaodong;Ominsky, Michael S.;Paszty, Chris
通讯作者：
Paszty, Chris
影响因子：
8.4
作者：
Jönsson, M;Borg, Å;Andersson, T
通讯作者：
Andersson, T
影响因子：
2.5
作者：
Hatsell, S;Rowlands, T;Cowin, P
通讯作者：
Cowin, P
DOI：
10.1007/bf02013227
发表时间：
1978-01-01
期刊：
CALCIFIED TISSUE RESEARCH
影响因子：
--
作者：
LIPS, P;COURPRON, P;MEUNIER, PJ
通讯作者：
MEUNIER, PJ