Phospholipase C Signaling via the Parathyroid Hormone (PTH)/PTH-Related Peptide Receptor Is Essential for Normal Bone Responses to PTH
Phospholipase C Signaling via the Parathyroid Hormone (PTH)/PTH-Related Peptide Receptor Is Essential for Normal Bone Responses to PTH
复制标题
DOI：
10.1210/en.2009-1494
复制
发表时间：
2010-08-01
期刊：
影响因子：
4.8
通讯作者：
Kronenberg, Henry M.
中科院分区：
文献类型：
--
作者：
Guo, Jun;Liu, Minlin;Kronenberg, Henry M.
我们以前已经表明，在表达突变的PTH/PTHrP受体（PTHR）（此处称为DSEL）的小鼠中，肥大软骨细胞的分化延迟，该受体正常刺激腺苷酸环化酶，但未能激活磷脂酶C（PLC）。为了更好地理解PLC信号通过PTHR在骨骼和矿物质稳态中的作用，我们检查了这些喂食正常或缺钙饮食的小鼠。在标准饮食中，DSEL小鼠显示出骨量的适度减少。值得注意的是，当喂食低钙饮食或注入PTH时，DSEL小鼠与Wt小鼠相比，表现出显著减少的小梁周围基质细胞反应和减弱的新骨形成。在来自喂食低钙饮食的DSEL小鼠的骨髓细胞中也观察到体外集落形成减弱。此外，甲状旁腺素刺激增殖和增加的mRNA编码细胞周期蛋白D1的主要成骨细胞来源于野生型，但不是从DSEL小鼠。我们的数据表明，PLC信号通过PTHR是骨骼的稳态所需的。（内分泌学151：3502-3513，2010）
We have previously shown that differentiation of hypertrophic chondrocytes is delayed in mice expressing a mutated PTH/PTHrP receptor (PTHR) (called DSEL here) that stimulates adenylyl cyclase normally but fails to activate phospholipase C (PLC). To better understand the role of PLC signaling via the PTHR in skeletal and mineral homeostasis, we examined these mice fed a normal or calcium-deficient diet. On a standard diet, DSEL mice displayed a modest decrease in bone mass. Remarkably, when fed a low-calcium diet or infused with PTH, DSEL mice exhibited strikingly curtailed peritrabecular stromal cell responses and attenuated new bone formation when compared with Wt mice. Attenuated in vitro colony formation was also observed in bone marrow cells derived from DSEL mice fed a low-calcium diet. Furthermore, PTH stimulated proliferation and increased mRNAs encoding cyclin D1 in primary osteoblasts derived from Wt but not from DSEL mice. Our data indicate that PLC signaling through the PTHR is required for skeletal homeostasis. (Endocrinology 151: 3502-3513, 2010)