Loss of the PGE2 receptor EP1 enhances bone acquisition, which protects against age and ovariectomy-induced impairments in bone strength.
Loss of the PGE2 receptor EP1 enhances bone acquisition, which protects against age and ovariectomy-induced impairments in bone strength.
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DOI：
10.1016/j.bone.2014.11.018
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发表时间：
2015-03
期刊：
影响因子：
4.1
通讯作者：
O'Keefe, Regis J.
中科院分区：
文献类型：
--
作者：
Zhang, Minjie;Feigenson, Marina;Sheu, Tzong-Jen;Awad, Hani A.;Schwarz, Edward M.;Jonason, Jennifer H.;Loiselle, Alayna E.;O'Keefe, Regis J.
PGE 2通过四种前列腺素受体（EP 1 -4）的独立作用对骨产生合成代谢和分解代谢作用。我们先前已经证明，EP 1的缺失通过促进骨形成来加速骨折修复。在本研究中，我们定义了EP 1在衰老过程中骨维持和稳态中的作用，以及对卵巢切除术的反应。在2个月、6个月和1岁时检查野生型（WT）和EP 1 −/−小鼠的股骨和L4椎骨，并在卵巢切除术（OVX）或假手术后检查WT和EP 1 −/−小鼠。与年龄匹配的WT小鼠相比，EP 1 −/−小鼠在衰老过程中更大程度地保持了骨体积分数、骨小梁结构和机械性能。此外，相对于WT，在EP 1 −/−中观察到骨形成率（BFR）（+60%）和矿物质沉积率（MAR）（+50%）显著增加，而破骨细胞数量和破骨细胞表面未观察到变化。在OVX后，EP 1的缺失对股骨和L4椎骨中的骨丢失具有保护作用，相对于WT OVX，骨体积/总体积（BV/TV）（股骨中+32%）和最大失效载荷（股骨中+10%）增加，这可能是由于在这些小鼠中观察到的骨形成速率增加。总而言之，这些研究确定抑制EP 1是抑制老年或绝经后患者骨丢失的潜在治疗方法。
PGE2 exerts anabolic and catabolic effects on bone through the discrete actions of four prostanoid receptors (EP1-4). We have previously demonstrated that loss EP1 accelerates fracture repair by enhancing bone formation. In the present study we defined the role of EP1 in bone maintenance and homeostasis during aging and in response to ovariectomy. The femur and L4 vertebrae of wild type (WT) and EP1−/− mice were examined at 2-months, 6-months, and 1-year of age, and in WT and EP1−/− mice following ovariectomy (OVX) or sham surgery. Bone volume fraction, trabecular architecture and mechanical properties were maintained during aging in EP1−/− mice to a greater degree than age-matched WT mice. Moreover, significant increases in bone formation rate (BFR) (+60%) and mineral apposition rate (MAR) (+50%) were observed in EP1−/−, relative to WT, while no change in osteoclast number and osteoclast surface were observed. Following OVX, loss of EP1 was protective against bone loss in both femur and L4 vertebrae, with increased bone volume/total volume (BV/TV) (+32% in femur) and max load at failure (+10% in femur) relative to WT OVX, likely resulting from the increased bone formation rate that was observed in these mice. Taken together these studies identify inhibition of EP1 as a potential therapeutic approach to suppress bone loss in aged or post-menopausal patients.
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影响因子：
64.5
作者：
Goessling W;North TE;Loewer S;Lord AM;Lee S;Stoick-Cooper CL;Weidinger G;Puder M;Daley GQ;Moon RT;Zon LI
通讯作者：
Zon LI
影响因子：
3.6
作者：
Machwate, M;Harada, S;Rodan, GA
通讯作者：
Rodan, GA
影响因子：
4.8
作者：
Fujino, H;West, KA;Regan, JW
通讯作者：
Regan, JW
影响因子：
3.7
作者：
Li, TF;Zuscik, MJ;O'Keefe, RJ
通讯作者：
O'Keefe, RJ
影响因子：
4.8
作者：
Mohan S;Glushakov AV;Decurnou A;Narumiya S;Doré S
通讯作者：
Doré S