Impaired 1,25-dihydroxyvitamin D3 action underlies enthesopathy development in the Hyp mouse model of X-linked hypophosphatemia.
Impaired 1,25-dihydroxyvitamin D3 action underlies enthesopathy development in the Hyp mouse model of X-linked hypophosphatemia.
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DOI：
10.1172/jci.insight.163259
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发表时间：
2023-09-08
期刊：
影响因子：
8
通讯作者：
Liu, Eva S.
中科院分区：
文献类型：
--
作者：
Rana, Rakshya;Baker, Jiana T.;Sorsby, Melissa;Jagga, Supriya;Venkat, Shreya;Almardini, Shaza;Liu, Eva S.
X连锁低磷血症（XLH）的特征是高血清成纤维细胞生长因子23（FGF 23）水平，导致1，25-二羟维生素D3（1，25 D）产生受损。患有XLH的成年人发展为肌腱-骨附着部位（附着点）的疼痛矿化，称为附着点病。用XLH（Hyp）与1，25 D或抗FGF 23 Ab治疗小鼠，这两者都增加1，25 D信号传导，预防末端病。因此，我们进行了研究，以确定受损的1，25 D作用在末端病发展中的作用。缺乏维生素D1 α-羟化酶（Cyp 27 b1）（C-/-）的小鼠的附着点具有与Hyp小鼠相似的附着点病，而Hyp小鼠中Fgf 23的缺失可预防附着点病，而小鼠中Cyp 27 b1和Fgf 23的缺失可导致附着点病，表明由于高FGF 23水平导致的1，25 D作用受损是XLH附着点病发展的基础。与Hyp小鼠一样，通过P14观察到C-/-小鼠中的末端病，并且用1，25 D治疗可以预防，但不能逆转。维生素D受体在巩膜表达细胞中的缺失导致附着点病变，表明1，25 D直接作用于附着点细胞以调节附着点病变的发展。这些结果表明，1，25 D信号是必要的正常出生后附着点成熟，并在XLH附着点病变的发展中发挥作用。在患有XLH的儿科患者中优化1，25 D置换是预防末端病的必要条件。
X-linked hypophosphatemia (XLH) is characterized by high serum fibroblast growth factor 23 (FGF23) levels, resulting in impaired 1,25-dihydroxyvitamin D3 (1,25D) production. Adults with XLH develop a painful mineralization of the tendon-bone attachment site (enthesis), called enthesopathy. Treatment of mice with XLH (Hyp) with 1,25D or an anti–FGF23 Ab, both of which increase 1,25D signaling, prevents enthesopathy. Therefore, we undertook studies to determine a role for impaired 1,25D action in enthesopathy development. Entheses from mice lacking vitamin D 1α-hydroxylase (Cyp27b1) (C–/–) had a similar enthesopathy to Hyp mice, whereas deletion of Fgf23 in Hyp mice prevented enthesopathy, and deletion of both Cyp27b1 and Fgf23 in mice resulted in enthesopathy, demonstrating that the impaired 1,25D action due to high FGF23 levels underlies XLH enthesopathy development. Like Hyp mice, enthesopathy in C–/– mice was observed by P14 and was prevented, but not reversed, with 1,25D therapy. Deletion of the vitamin D receptor in scleraxis-expressing cells resulted in enthesopathy, indicating that 1,25D acted directly on enthesis cells to regulate enthesopathy development. These results show that 1,25D signaling was necessary for normal postnatal enthesis maturation and played a role in XLH enthesopathy development. Optimizing 1,25D replacement in pediatric patients with XLH is necessary to prevent enthesopathy.
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影响因子：
7.3
作者：
Killian ML
通讯作者：
Killian ML
影响因子：
6.2
作者：
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通讯作者：
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DOI：
10.1002/jbmr.3938
发表时间：
2020-04
期刊：
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
影响因子：
--
作者：
Kotwal A;Ferrer A;Kumar R;Singh RJ;Murthy V;Schultz-Rogers L;Zimmermann M;Lanpher B;Zimmerman K;Stabach PR;Klee E;Braddock DT;Wermers RA
通讯作者：
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影响因子：
3.7
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Fu B;Wang H;Wang J;Barouhas I;Liu W;Shuboy A;Bushinsky DA;Zhou D;Favus MJ
通讯作者：
Favus MJ
DOI：
10.1073/pnas.0503617102
发表时间：
2005-12-13
影响因子：
11.1
作者：
Kobayashi, T;Lyons, KM;Kronenberg, HM
通讯作者：
Kronenberg, HM