转录因子 Runx2 在青少年特发性脊柱侧凸女孩低骨密度中的作用。
Transcription factor Runx2 in the low bone mineral density of girls with adolescent idiopathic scoliosis.
机构信息
Department of Spine Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
出版信息
Orthop Surg. 2014 Feb;6(1):8-14. doi: 10.1111/os.12087.
OBJECTIVE
The molecular mechanism of low bone mass in girls with adolescent idiopathic scoliosis (AIS) has not been ascertained. Runx2 is a critical transcription factor regulating osteoblast differentiation and maturation. The present study aimed to explore the possible relationship between Runx2 expression in osteoblasts and bone mineral density (BMD) in subjects with AIS.
METHODS
Twenty-two girls with AIS scheduled to corrective surgery with iliac crest as donor site of autograft for spinal fusion were recruited. The BMD of lumbar spine and femoral neck were assessed by dual-energy X-ray absorptiometry, then patients were divided into two groups with either normal or reduced BMD. Cancellous bone was harvested from their iliac crests for primary culture of osteoblasts. mRNA and protein expression of Runx2 were assayed by reverse transcription-polymerase chain reaction and western blotting, respectively. Results were compared between the two groups and correlated with BMD.
RESULTS
AIS patients with normal BMD showed comparable maturity and body mass index but significant lower Cobb angle of main curve than those of patients with reduced BMD. The mean BMD of lumbar spine and femoral neck were 0.993 g/m(2) and 0.911 g/m(2) in patients with normal BMD, and were 0.757 g/m(2) and 0.733 g/m(2) in those with reduced BMD, respectively. The differences were significant between two groups (P < 0.05). The relative mean mRNA and protein expression of Runx2 were 0.49 ± 0.12 and 0.062 ± 0.020 in AIS with normal BMD, 0.35 ± 0.12 and 0.042 ± 0.006 in AIS with reduced BMD, respectively. Significantly lower Runx2 mRNA and protein expression were found in patients with AIS patients with reduced BMD than in those with normal BMD (P < 0.05). After controlling for age, weight and body mass index, positive correlations were found between Runx2 expression of both mRNA and protein and BMD of lumbar spine and femoral neck.
CONCLUSION
The abnormal expression of Runx2 in patients with AIS and reduced BMD indicates abnormal regulation of differentiation of their osteoblasts. Runx2 may play an important role in the pathogenesis of reduced BMD in patients with AIS.
目的
尚未明确青少年特发性脊柱侧凸（AIS）女孩低骨量的分子机制。Runx2 是调节成骨细胞分化和成熟的关键转录因子。本研究旨在探讨 AIS 患者成骨细胞中 Runx2 表达与骨密度（BMD）之间的可能关系。
方法
招募了 22 名计划接受矫正手术的 AIS 女孩，取其髂嵴作为脊柱融合自体移植物的供体部位。通过双能 X 射线吸收法评估腰椎和股骨颈的 BMD，然后将患者分为 BMD 正常组和 BMD 降低组。从髂嵴采集松质骨，进行成骨细胞的原代培养。通过逆转录聚合酶链反应和蛋白质印迹法分别检测 Runx2 的 mRNA 和蛋白表达，比较两组之间的结果，并与 BMD 相关联。
结果
BMD 正常的 AIS 患者的成熟度和体重指数相当，但主弯 Cobb 角显著低于 BMD 降低的患者。BMD 正常的患者腰椎和股骨颈的平均 BMD 分别为 0.993 g/m2 和 0.911 g/m2，BMD 降低的患者分别为 0.757 g/m2 和 0.733 g/m2，两组间差异有统计学意义（P<0.05）。BMD 正常的 AIS 患者的 Runx2 相对平均 mRNA 和蛋白表达分别为 0.49±0.12 和 0.062±0.020，BMD 降低的 AIS 患者分别为 0.35±0.12 和 0.042±0.006，BMD 降低的患者的 Runx2 mRNA 和蛋白表达明显低于 BMD 正常的患者（P<0.05）。在校正年龄、体重和体重指数后，Runx2 的 mRNA 和蛋白表达与腰椎和股骨颈的 BMD 呈正相关。
结论
AIS 患者中 Runx2 的异常表达以及 BMD 的降低表明其成骨细胞分化的异常调节。Runx2 可能在 AIS 患者 BMD 降低的发病机制中发挥重要作用。
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