Estradiol and RSPO3 regulate vertebral trabecular bone mass independent of each other.
Estradiol and RSPO3 regulate vertebral trabecular bone mass independent of each other.
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DOI：
10.1152/ajpendo.00383.2021
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发表时间：
2022-03-01
期刊：
影响因子：
--
通讯作者：
Movérare-Skrtic S
中科院分区：
文献类型：
--
作者：
Nilsson KH;Wu J;Gustafsson KL;El Shahawy M;Koskela A;Tuukkanen J;Tuckermann J;Henning P;Lerner UH;Ohlsson C;Movérare-Skrtic S
骨质疏松症是一种年龄依赖性的严重骨骼疾病，导致患者的巨大痛苦和高昂的社会成本，特别是随着全球人口达到更高的年龄。绝经后雌激素水平下降导致大量骨质流失和骨折风险增加，而雌激素治疗可改善女性骨量。RSPO 3是一种调节WNT信号传导的分泌蛋白，可增加小鼠椎骨的骨小梁质量和强度，并与人类的骨小梁密度和前臂远端骨折风险相关。本研究的目的是确定RSPO 3是否参与雌激素的骨保护作用。我们首先观察到，雌二醇（E2）治疗增加卵巢切除（OVX）小鼠骨中RSPO 3的表达，支持RSPO 3在雌激素的骨保护作用中的可能作用。由于RSPO 3主要由骨中的成骨细胞表达，因此我们使用缺乏成骨细胞衍生的RSPO 3的小鼠模型（Runx 2-creRspo 3flox/flox小鼠）来确定RSPO 3是否是OVX小鼠中E2的骨保护作用所必需的。我们证实，成骨细胞特异性RSPO 3失活导致椎骨中骨小梁质量和强度的大幅降低。然而，在缺乏成骨细胞衍生的RSPO 3的小鼠和对照小鼠中，E2增加了椎体骨小梁的质量和强度。出乎意料的是，需要成骨细胞衍生的RSPO 3对皮质骨厚度的完全雌激素反应。总之，虽然成骨细胞衍生的RSPO 3是脊椎骨小梁的重要调节因子，但它是OVX小鼠皮质骨（而非骨小梁）的完全雌激素效应所必需的。因此，雌二醇和RSPO 3相互独立地调节椎骨骨小梁骨量。新&值得注意的是，成骨细胞衍生的RSPO 3是脊椎骨小梁的重要调节因子。我们的新发现表明，RSPO 3和雌激素调节骨小梁相互独立，但RSPO 3是必要的皮质骨的完整的雌激素效应。
Osteoporosis is an age-dependent serious skeletal disease that leads to great suffering for the patient and high social costs, especially as the global population reaches higher age. Decreasing estrogen levels after menopause result in a substantial bone loss and increased fracture risk, whereas estrogen treatment improves bone mass in women. RSPO3, a secreted protein that modulates WNT signaling, increases trabecular bone mass and strength in the vertebrae of mice, and is associated with trabecular density and risk of distal forearm fractures in humans. The aim of the present study was to determine if RSPO3 is involved in the bone-sparing effect of estrogens. We first observed that estradiol (E2) treatment increases RSPO3 expression in bone of ovariectomized (OVX) mice, supporting a possible role of RSPO3 in the bone-sparing effect of estrogens. As RSPO3 is mainly expressed by osteoblasts in the bone, we used a mouse model devoid of osteoblast-derived RSPO3 (Runx2-creRspo3flox/flox mice) to determine if RSPO3 is required for the bone-sparing effect of E2 in OVX mice. We confirmed that osteoblast-specific RSPO3 inactivation results in a substantial reduction in trabecular bone mass and strength in the vertebrae. However, E2 increased vertebral trabecular bone mass and strength similarly in mice devoid of osteoblast-derived RSPO3 and control mice. Unexpectedly, osteoblast-derived RSPO3 was needed for the full estrogenic response on cortical bone thickness. In conclusion, although osteoblast-derived RSPO3 is a crucial regulator of vertebral trabecular bone, it is required for a full estrogenic effect on cortical, but not trabecular, bone in OVX mice. Thus, estradiol and RSPO3 regulate vertebral trabecular bone mass independent of each other. NEW & NOTEWORTHY Osteoblast-derived RSPO3 is known to be a crucial regulator of vertebral trabecular bone. Our new findings show that RSPO3 and estrogen regulate trabecular bone independent of each other, but that RSPO3 is necessary for a complete estrogenic effect on cortical bone.
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影响因子：
82.9
作者：
通讯作者：
--
影响因子：
4.6
作者：
Bandeira, Leonardo;Lewiecki, E. Michael;Bilezikian, John P.
通讯作者：
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影响因子：
7.7
作者：
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影响因子：
5.4
作者：
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通讯作者：
Monroe DG
影响因子：
5.8
作者：
Baron, Roland;Hesse, Eric
通讯作者：
Hesse, Eric