Department of Spine Surgery, Xiangya Hospital of Central-South University, Changsha, 410008, Hunan, China.
J Transl Med. 2019 Feb 28;17(1):64. doi: 10.1186/s12967-019-1805-7.
Osteopenia have been well documented in adolescent idiopathic scoliosis (AIS). Adiponectin has been shown to be inversely proportional to body mass index and to affect bone metabolism. However, the circulating levels of adiponectin and the relationship between adiponectin and low bone mass in AIS remain unclear.
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 adiponectin levels were determined by enzyme-linked immunosorbent assay (ELISA) in the AIS and control groups. An improved multiplex ligation detection reaction was performed to study on single nucleotide polymorphism. Facet joints were collected and used to measure the microstructure, the expression of RANKL, OPG, osteoblast-related genes, inflammatory factors, adiponectin and its receptors by qPCR, western blotting and immunohistochemistry. Furthermore, primary cells were extracted from facet joints to observe the reaction after adiponectin stimulation.
RESULTS: Compared with the controls, lower body mass index and a marked increase in circulating adiponectin were observed in AIS osteopenia (17.09 ± 1.09 kg/m and 21.63 ± 10.30 mg/L). A significant difference in the presence of rs7639352 was detected in the AIS osteopenia, AIS normal bone mass and control groups. The T allele showed a significant higher proportion in AIS osteopenia than AIS normal bone mass and control groups (41.75% vs 31.3% vs 25.7%, p < 0.05). micro-CT demonstrated that the AIS convex side had a significant lower bone volume than concave side. RNA and protein analyses showed that in cancellous bone, higher RANKL/OPG and adipoR1 levels and lower runx2 levels were observed, and in cartilage, higher adipoR1 and IL6 levels were observed in AIS. Furthermore, convex side had higher RANKL/OPG, IL6 and adipoR1 than concave side. Compared with normal primary cells, convex side primary cells showed the most acute action, and concave side primary cells showed the second-most acute action when exposed under same adiponectin concentration gradient.
Our results indicated that high circulating adiponectin levels may result from gene variations in AIS osteopenia. Adiponectin has a negative effect on bone metabolism, and this negative effect might be mediated by the ADR1-RANKL/OPG and ADR1-IL6 pathways.
青少年特发性脊柱侧凸（AIS）患者的骨量减少已得到充分证实。脂联素与体重指数呈负相关，并影响骨代谢。然而，AIS 患者的脂联素循环水平及其与低骨量的关系尚不清楚。
本研究共纳入 563 例 AIS 患者和 281 例年龄匹配的对照组。所有参与者均进行人体测量和骨量测定。采用酶联免疫吸附试验（ELISA）测定 AIS 组和对照组的血浆脂联素水平。采用改良的多重连接检测反应分析单核苷酸多态性。收集小关节，通过 qPCR、western blot 和免疫组化检测 RANKL、OPG、成骨细胞相关基因、炎症因子、脂联素及其受体的表达。此外，从小关节中提取原代细胞，观察脂联素刺激后的反应。
与对照组相比，AIS 骨量减少患者的体重指数较低，循环脂联素明显升高（17.09±1.09kg/m 和 21.63±10.30mg/L）。在 AIS 骨量减少、AIS 正常骨量和对照组中，rs7639352 的存在存在显著差异。T 等位基因在 AIS 骨量减少患者中的比例明显高于 AIS 正常骨量和对照组（41.75%比 31.3%比 25.7%，p<0.05）。Micro-CT 显示 AIS 凸侧的骨体积明显低于凹侧。RNA 和蛋白质分析显示，在松质骨中，RANKL/OPG 和 adipoR1 水平升高，runx2 水平降低，在软骨中，adipoR1 和 IL6 水平升高。此外，凸侧的 RANKL/OPG、IL6 和 adipoR1 均高于凹侧。与正常原代细胞相比，在相同的脂联素浓度梯度下，凸侧原代细胞的反应最为剧烈，而凹侧原代细胞的反应次之。
我们的结果表明，AIS 骨量减少患者的高循环脂联素水平可能是由于基因变异所致。脂联素对骨代谢有负向作用，这种负向作用可能是通过 ADR1-RANKL/OPG 和 ADR1-IL6 途径介导的。
