Drexel University College of Medicine, Philadelphia, PA, United States.
Department of Rehabilitation Medicine, University of Minnesota School of Medicine, Minneapolis, MN, United States.
Front Endocrinol (Lausanne). 2022 Aug 5;13:910934. doi: 10.3389/fendo.2022.910934. eCollection 2022.
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.
脊髓损伤常伴有骨质疏松症，其特征是骨量迅速和严重流失。这导致脊髓损伤患者发生骨质疏松性骨折的风险增加，从而增加医疗保健成本、发病率和死亡率。尽管这种情况很常见，但导致这种骨质疏松症的机制尚不完全清楚，治疗选择也有限。目前尚未确定用于预测骨折风险的生物标志物。在这项研究中，我们试图研究与脊髓损伤后骨质疏松症相关的 microRNA 介导的机制。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）受试者。所有受试者的血浆样本均进行了转录组分析，以定量 microRNA 表达，之后选择 miR-148a-3p 进行进一步研究。我们对所有脊髓损伤受试者进行了膝关节 CT 扫描，并对这些扫描进行了分析，以定量骨髓脂肪组织体积。与慢性 SCI 相比，急性 SCI 受试者以及急性 SCI 与无 SCI 相比，miR-148a-3p 表达上调。与急性 SCI 受试者相比，慢性 SCI 受试者的远端股骨骨干骨髓脂肪含量更高。miR-148a-3p 水平与远端股骨骨干骨髓脂肪含量呈负相关。多变量模型显示，miR-148a-3p 和 BMI 可以解释骨髓脂肪含量变化的 24%。文献检索显示，miR-148a-3p 有多个与骨和脂肪代谢相关的靶标。我们的研究结果表明，miR-148a-3p 是脊髓损伤后骨质疏松症的一种介质，也是未来潜在的治疗靶点。
