BACKGROUND Osteopenia has been well documented in adolescent idiopathic scoliosis (AIS), and ghrelin has been shown to have a positive effect on bone metabolism. However, the circulating level of ghrelin is increased in AIS osteopenia, and the relationship between ghrelin and low bone mass in AIS osteopenia remains unclear. METHOD A total of 563 AIS and 281 age-matched controls were recruited for this study. Anthropometry and bone mass were measured in all participants. Plasma ghrelin levels were determined by enzyme-linked immunosorbent assay (ELISA) in both AIS and control groups. An improved multiplex ligation detection reaction was performed to analyze single-nucleotide polymorphisms (SNPs). Facet joints were collected and subjected to immunohistochemistry; osteogenic gene and protein expression was also measured. Furthermore, primary cells were extracted from facet joints and bone marrow to observe the response to ghrelin stimulation. RESULTS The body mass index was lower and circulating ghrelin was markedly higher in the AIS osteopenia group than in the control group. No significant difference was observed in four ghrelin level-related SNPs between the AIS osteopenia and control groups. RNA and protein analyses revealed higher RANKL/OPG and lower runx2 levels in AIS cancellous bone. Compared with normal primary osteoblasts and BMSCs, AIS osteopenia primary cells were insensitive to the same ghrelin concentration gradient and showed lower osteogenic ability, increases in OPG and decreases in RANKL. CONCLUSION Our results indicate that high circulating ghrelin levels may not result from gene variations in AIS osteopenia. Dysregulation of the ghrelin/RANKL/OPG pathway may lead to decreased osteogenic ability of osteoblasts and BMSCs, which may be related to lower bone mass in AIS osteopenia.

中文翻译：

---

骨量中ghrelin/RANKL/OPG通路的失调与AIS骨质减少有关

背景 青少年特发性脊柱侧弯 (AIS) 中的骨质减少已得到充分证明，并且生长素释放肽已被证明对骨代谢具有积极影响。然而，AIS 骨量减少时 ghrelin 的循环水平升高，且 AIS 骨量减少时生长素释放肽与低骨量之间的关系尚不清楚。方法 本研究共招募了 563 名 AIS 和 281 名年龄匹配的对照。测量所有参与者的人体测量学和骨量。通过酶联免疫吸附试验 (ELISA) 在 AIS 和对照组中测定血浆生长素释放肽水平。进行了改进的多重连接检测反应以分析单核苷酸多态性 (SNP)。收集小关节并进行免疫组化；还测量了成骨基因和蛋白质的表达。此外，从小关节和骨髓中提取原代细胞以观察对生长素释放肽刺激的反应。结果 与对照组相比，AIS 骨质减少组的体重指数较低，循环生长素释放肽显着升高。在 AIS 骨质减少症组和对照组之间的四个生长素释放肽水平相关的 SNP 中没有观察到显着差异。RNA 和蛋白质分析显示 AIS 松质骨中更高的 RANKL/OPG 和更低的 runx2 水平。与正常原代成骨细胞和 BMSC 相比，AIS 骨质减少原代细胞对相同的 ghrelin 浓度梯度不敏感，并表现出较低的成骨能力、OPG 增加和 RANKL 降低。结论 我们的结果表明高循环生长素释放肽水平可能不是由 AIS 骨质减少的基因变异引起的。