MicroRNA-148a-3p is a candidate mediator of increased bone marrow adiposity and bone loss following spinal cord injury.

MicroRNA-148a-3p is a candidate mediator of increased bone marrow adiposity and bone loss following spinal cord injury.
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DOI:
10.3389/fendo.2022.910934
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发表时间:
2022
影响因子:
5.2
通讯作者:
Battaglino RA
Battaglino RA
中科院分区:
医学2区
文献类型:
--
作者:
Lincoln S;Morse LR;Troy K;Mattson N;Nguyen N;Battaglino RA

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脊髓损伤后常伴有骨质疏松症,其特征是迅速而严重的骨质丢失。这会导致脊髓损伤患者发生骨质疏松性骨折的风险增加,从而增加医疗费用、发病率和死亡率。虽然这很常见,但这种骨质疏松症的机制并不完全清楚,治疗选择也很有限。目前还没有发现可以预测骨折风险的生物标志物。在这项研究中,我们试图研究microRNA介导的与脊髓损伤后骨质疏松症相关的机制。我们研究了急性脊髓损伤(n=12)、慢性脊髓损伤(n=18)和无脊髓损伤的对照组(n=23)。所有受试者的血浆样本都进行了转录转录分析以量化microRNA的表达,然后选择miR-148A-3p进行进一步研究。我们对所有患有脊髓损伤的受试者进行了膝关节CT扫描,并分析了这些扫描以量化骨髓脂肪组织的体积。MIR-148A-3p在急性SCI组和慢性SCI组以及急性SCI组和非SCI组均有上调。与急性脊髓损伤患者相比,慢性脊髓损伤患者股骨干远端的骨髓肥厚程度更高。MIR-148A-3p水平与股骨干远端骨髓肥厚呈负相关。多变量模型显示miR-148A-3p和BMI可以解释24%的骨髓肥胖症变异。文献检索显示miR-148A-3P具有多个骨和脂肪代谢相关靶点。我们的发现提示miR-148A-3p是脊髓损伤后骨质疏松的介质,也是未来潜在的治疗靶点。
Spinal cord injury is often followed by osteoporosis characterized by rapid and severe bone loss. This leads to an increased risk of osteoporotic fracture in people with spinal cord injury, resulting in increased healthcare costs, morbidity, and mortality. Though it is common, the mechanisms underlying this osteoporosis are not completely understood and treatment options are limited. No biomarkers have been identified for predicting fracture risk. In this study, we sought to investigate microRNA mediated mechanisms relating to osteoporosis following spinal cord injury. We studied subjects with acute SCI (n=12), chronic SCI (n=18), and controls with no SCI (n=23). Plasma samples from all subjects underwent transcriptomic analysis to quantify microRNA expression, after which miR-148a-3p was selected for further study. We performed CT scans of the knee on all subjects with SCI and analyzed these scans to quantify bone marrow adipose tissue volume. MiR-148a-3p was upregulated in subjects with acute SCI vs chronic SCI, as well as in acute SCI vs no SCI. Subjects with chronic SCI had greater levels of marrow adiposity in the distal femoral diaphysis compared to subjects with acute SCI. MiR-148a-3p levels were negatively associated with distal femoral diaphysis marrow adiposity. A multivariable model showed that miR-148a-3p and BMI explained 24% of variation in marrow adiposity. A literature search revealed that miR-148a-3p has multiple bone and fat metabolism related targets. Our findings suggest that miR-148a-3p is a mediator of osteoporosis following spinal cord injury and a potential future therapeutic target.
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