Effect of age on regulation of human osteoclast differentiation.
Effect of age on regulation of human osteoclast differentiation.
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DOI：
10.1002/jcb.24792
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发表时间：
2014-08
影响因子：
4
通讯作者：
Glowacki, Julie
中科院分区：
文献类型：
--
作者：
Chung, Ping-Lin;Zhou, Shuanhu;Eslami, Behnam;Shen, Longxiang;LeBoff, Meryl S.;Glowacki, Julie
人类骨骼老化的特征是由于过量的骨吸收不能被新骨形成所平衡而导致骨量的逐渐损失。使用人骨髓细胞，我们检验了以下假设：由于调节因子[巨噬细胞集落刺激因子（M-CSF）、NF-κB配体受体激活因子（RANKL）和骨保护素（OPG）]及其受体[c-fms和RANK]的内在变化，破骨细胞生成呈年龄依赖性增加。在骨髓细胞（BMC）中，c-fms（r=0.61，p=0.006）和RANK表达（r=0.59，p=0.008）随年龄增加（27-82岁，n=19）。体外破骨细胞生成随年龄增长而增加（r=0.89，p=0.007）。在富集的骨髓基质细胞（MSCs）中，RANKL的组成性表达随年龄增加而增加（r=0.41，p=0.049），OPG的表达与年龄呈负相关（r=-0.43，p =0.039）。因此，RANKL/OPG存在年龄相关性增加（r=0.56，p=0.005）。这些数据表明，人破骨细胞生成的年龄相关性增加与破骨细胞祖细胞中c-fms和RANK表达的内在增加相关，并且在支持MSC中，促破骨细胞生成RANKL表达增加和抗破骨细胞生成OPG减少。这些发现支持了人类骨髓细胞及其产物通过增加骨吸收破骨细胞的产生而促进骨骼衰老的假设。这些发现有助于解释人类随着年龄增长而进行性骨丢失的潜在分子机制。
Human skeletal aging is characterized as a gradual loss of bone mass due to an excess of bone resorption not balanced by new bone formation. Using human marrow cells, we tested the hypothesis that there is an age-dependent increase in osteoclastogenesis due to intrinsic changes in regulatory factors [macrophage-colony stimulating factor (M-CSF), receptor activator of NF-κB ligand (RANKL), and osteoprotegerin (OPG)] and their receptors [c-fms and RANK]. In bone marrow cells (BMCs), c-fms (r=0.61, p=0.006) and RANK expression (r=0.59, p=0.008) were increased with age (27-82 years, n=19). In vitro generation of osteoclasts was increased with age (r=0.89, p=0.007). In enriched marrow stromal cells (MSCs), constitutive expression of RANKL was increased with age (r=0.41, p=0.049) and expression of OPG was inversely correlated with age (r=-0.43, p=0.039). Accordingly, there was an age-related increase in RANKL/OPG (r=0.56, p=0.005). These data indicate an age-related increase in human osteoclastogenesis that is associated with an intrinsic increase in expression of c-fms and RANK in osteoclast progenitors, and, in the supporting MSCs, an increase in pro-osteoclastogenic RANKL expression and a decrease in anti-osteoclastogenic OPG. These findings support the hypothesis that human marrow cells and their products can contribute to skeletal aging by increasing the generation of bone-resorbing osteoclasts. These findings help to explain underlying molecular mechanisms of progressive bone loss with advancing age in humans.
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影响因子：
2.8
作者：
Jiang, Ying;Mishima, Hajime;Uemura, Toshimasa
通讯作者：
Uemura, Toshimasa
影响因子：
4.2
作者：
Eriksen, Charlotte Grith;Olsen, Helene;Langdahl, Bente Lomholt
通讯作者：
Langdahl, Bente Lomholt
影响因子：
4.2
作者：
Abdallah, BM;Stilgren, LS;Abrahamsen, B
通讯作者：
Abrahamsen, B
影响因子：
82.9
作者：
Nakashima, Tomoki;Hayashi, Mikihito;Takayanagi, Hiroshi
通讯作者：
Takayanagi, Hiroshi
影响因子：
6.2
作者：
Atkins, GJ;Haynes, DR;Findlay, DM
通讯作者：
Findlay, DM