Control of bone mass and remodeling by PTH receptor signaling in osteocytes.
Control of bone mass and remodeling by PTH receptor signaling in osteocytes.
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DOI：
10.1371/journal.pone.0002942
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发表时间：
2008-08-13
期刊：
影响因子：
3.7
通讯作者：
Bellido T
中科院分区：
文献类型：
--
作者：
O'Brien CA;Plotkin LI;Galli C;Goellner JJ;Gortazar AR;Allen MR;Robling AG;Bouxsein M;Schipani E;Turner CH;Jilka RL;Weinstein RS;Manolagas SC;Bellido T
骨细胞，前成骨细胞埋在骨，被认为是协调骨骼适应机械刺激。然而，激素是否通过作用于骨细胞来控制骨骼的动态平衡仍不清楚。甲状旁腺激素（PTH）刺激骨重建，并可能导致骨丢失或骨获得，这取决于骨吸收和骨形成之间的平衡。在此，我们证明，转基因小鼠表达的组成型活性PTH受体专门在骨细胞表现出增加骨量和骨重建，以及减少表达的骨细胞衍生的Wnt拮抗剂sclerostin，增加Wnt信号，增加破骨细胞和成骨细胞数量，减少成骨细胞凋亡。Wnt共受体LDL相关受体5（LRP 5）的缺失减弱高骨量表型，但不减弱转基因诱导的骨重塑的增加。这些发现表明，骨细胞中的PTH受体信号传导分别通过LRP 5依赖性和非依赖性机制增加骨量和骨重建速率。
Osteocytes, former osteoblasts buried within bone, are thought to orchestrate skeletal adaptation to mechanical stimuli. However, it remains unknown whether hormones control skeletal homeostasis through actions on osteocytes. Parathyroid hormone (PTH) stimulates bone remodeling and may cause bone loss or bone gain depending on the balance between bone resorption and formation. Herein, we demonstrate that transgenic mice expressing a constitutively active PTH receptor exclusively in osteocytes exhibit increased bone mass and bone remodeling, as well as reduced expression of the osteocyte-derived Wnt antagonist sclerostin, increased Wnt signaling, increased osteoclast and osteoblast number, and decreased osteoblast apoptosis. Deletion of the Wnt co-receptor LDL related receptor 5 (LRP5) attenuates the high bone mass phenotype but not the increase in bone remodeling induced by the transgene. These findings demonstrate that PTH receptor signaling in osteocytes increases bone mass and the rate of bone remodeling through LRP5-dependent and -independent mechanisms, respectively.
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DOI：
10.1073/pnas.0505259102
发表时间：
2005-11-29
影响因子：
11.1
作者：
Clément-Lacroix, P;Ai, MR;Rawadi, G
通讯作者：
Rawadi, G
影响因子：
6.2
作者：
Chen, XS;Macica, CM;Broadus, AE
通讯作者：
Broadus, AE
影响因子：
64.5
作者：
Gong, YQ;Slee, RB;Warman, ML
通讯作者：
Warman, ML
影响因子：
15.9
作者：
Jilka, RL;Weinstein, RS;Manolagas, SC
通讯作者：
Manolagas, SC
影响因子：
--
作者：
Bodine, PVN;Zhao, WG;Komm, BS
通讯作者：
Komm, BS