Mice with a heterozygous Lrp6 deletion have impaired fracture healing.
Mice with a heterozygous Lrp6 deletion have impaired fracture healing.
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DOI：
10.1038/boneres.2016.25
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发表时间：
2016
期刊：
影响因子：
12.7
通讯作者：
Williams, Bart O.
中科院分区：
文献类型：
--
作者：
Burgers, Travis A.;Vivanco, Juan F.;Zahatnansky, Juraj;Moren, Andrew J. Vander;Mason, James J.;Williams, Bart O.
骨折不愈合，即骨折不能愈合，发生在10%-20%的骨折中，是一个昂贵且使人虚弱的临床问题。Wnt/β-连环蛋白通路在骨骼发育和骨折愈合过程中起关键作用。连接低密度脂蛋白受体相关蛋白6(LRP6)是一种Wnt结合受体，它的多态性与骨密度降低和脆性骨折有关，尽管这一点仍然存在争议。LRP6纯合子缺失的小鼠有严重的骨骼异常，无法存活，而杂合缺失的小鼠与LRP5有降低骨密度的联合作用。由于骨折愈合与胚胎骨骼发育密切相关，我们研究了LRP6杂合(LRP6+/−)小鼠的骨折愈合过程，并假设LRP6杂合缺失会损害骨折愈合。建立LRP6+/−小鼠和野生型对照(LRP6+/+)股骨中段骨折模型。使用微型计算机断层扫描(μCT)、生物力学测试和组织学分析对骨折进行分析。LRP6+/−小鼠在骨折后28d的骨痂硬度和强度显著降低，在骨折后第14天和-21d显著降低骨痂的骨密度、骨密度、骨密度和骨痂成熟面积，在骨折后第14天和21d显著增加空骨痂面积。我们的结果表明，LRP6杂合性缺失损害了骨折的愈合，这表明LRP6在骨折愈合中具有一定的作用。
Bone fracture non-unions, the failure of a fracture to heal, occur in 10%–20% of fractures and are a costly and debilitating clinical problem. The Wnt/β-catenin pathway is critical in bone development and fracture healing. Polymorphisms of linking low-density lipoprotein receptor-related protein 6 (LRP6), a Wnt-binding receptor, have been associated with decreased bone mineral density and fragility fractures, although this remains controversial. Mice with a homozygous deletion of Lrp6 have severe skeletal abnormalities and are not viable, whereas mice with a heterozygous deletion have a combinatory effect with Lrp5 to decrease bone mineral density. As fracture healing closely models embryonic skeletal development, we investigated the process of fracture healing in mice heterozygous for Lrp6 (Lrp6 +/−) and hypothesized that the heterozygous deletion of Lrp6 would impair fracture healing. Mid-diaphyseal femur fractures were induced in Lrp6 +/− mice and wild-type controls (Lrp6 +/+). Fractures were analyzed using micro-computed tomography (μCT) scans, biomechanical testing, and histological analysis. Lrp6 +/− mice had significantly decreased stiffness and strength at 28 days post fracture (PF) and significantly decreased BV/TV, total density, immature bone density, and mature area within the callus on day-14 and -21 PF; they had significantly increased empty callus area at days 14 and 21 PF. Our results demonstrate that the heterozygous deletion of Lrp6 impairs fracture healing, which suggests that Lrp6 has a role in fracture healing.
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影响因子：
5.6
作者：
Gaur, Tripti;Wixted, John J.;Hussain, Sadiq;O'Connell, Shannon L.;Morgan, Elise F.;Ayers, David C.;Komm, Barry S.;Bodine, Peter V.;Stein, Gary S.;Lian, Jane B.
通讯作者：
Lian, Jane B.
影响因子：
2.7
作者：
Joeng KS;Schumacher CA;Zylstra-Diegel CR;Long F;Williams BO
通讯作者：
Williams BO
DOI：
10.1615/critreveukargeneexpr.v20.i2.20
发表时间：
2010
影响因子：
1.6
作者：
Coulibaly MO;Sietsema DL;Burgers TA;Mason J;Williams BO;Jones CB
通讯作者：
Jones CB
影响因子：
15.8
作者：
Chen Y;Whetstone HC;Lin AC;Nadesan P;Wei Q;Poon R;Alman BA
通讯作者：
Alman BA
影响因子：
3.1
作者：
Hugunin, Kelly M. S.;Fry, Christopher;Nemzek, Jean A.
通讯作者：
Nemzek, Jean A.