Department of Orthopaedics and Traumatology, SH Ho Scoliosis Research Laboratory, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR, China.
Joint Scoliosis Research Centre of the Chinese University of Hong Kong and Nanjing University, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR, China.
Stud Health Technol Inform. 2021 Jun 28;280:23-28. doi: 10.3233/SHTI210427.
Adolescent Idiopathic Scoliosis (AIS) occurs during pubertal rapid growth period and is closely associated with low bone mass. The underlying mechanisms for systemic low bone mass in AIS remains unclear. Wnt signalling pathway is one of the important pathways regulating bone metabolism and influencing bone strength, its family member Wnt16 associates with lower bone mineral density (BMD) in late adulthood, and plays key regulatory role in determining cortical bone quality in adult mice. Our randomized control trial have reported vitamin D (VitD) supplementation significantly improved bone mass and reduced the risk of curve progression in AIS. A case-control study and animal study were employed to answer if WNT16 is associated with the abnormal bone quality in AIS and if the effect of VitD supplementation is associated with Wnt16, respectively. A cohort of 161 AIS and control female subjects were recruited for measurement of anthropometric parameters, bone qualities, and circulating Wnt16 level. In animal study, WT and Wnt16 gKO mice were both subjected to special VitD diet from week 4 and terminated at week 7 and 10 for samples harvesting. AIS showed significantly lower BMD, circulating WNT16 level, and elevated serum level of type I procollagen N-terminal propeptide. Wnt16 gKO mice demonstrated lower cortical bone density compared with WT mice from week 7 of age and Wnt16 gKO were less prone to cortical bone loss induced by high dosage VitD diet. Further study on the biological role of WNT16 and crosstalk with VitD metabolism on bone qualities is warranted which might shed light on prognostic gene of osteopenia and new perspectives for potential target to prevent curve progression.
青少年特发性脊柱侧凸（AIS）发生在青春期快速生长期间，与低骨量密切相关。AIS 中全身低骨量的潜在机制尚不清楚。Wnt 信号通路是调节骨代谢和影响骨强度的重要途径之一，其家族成员 Wnt16 与成年后期的低骨矿物质密度（BMD）相关，并在成年小鼠确定皮质骨质量方面发挥关键调节作用。我们的随机对照试验报告称，维生素 D（VitD）补充剂可显著改善骨量并降低 AIS 曲线进展的风险。一项病例对照研究和动物研究分别用于回答 WNT16 是否与 AIS 中的异常骨质量相关，以及 VitD 补充是否与 Wnt16 相关。一项纳入 161 名 AIS 和对照女性受试者的队列研究用于测量人体测量参数、骨质量和循环 Wnt16 水平。在动物研究中，WT 和 Wnt16 gKO 小鼠均从第 4 周开始接受特殊的 VitD 饮食，并在第 7 周和第 10 周结束时进行样本采集。AIS 表现出明显较低的 BMD、循环 WNT16 水平和升高的 I 型前胶原 N 端前肽血清水平。从 7 周龄开始，Wnt16 gKO 小鼠的皮质骨密度明显低于 WT 小鼠，并且 Wnt16 gKO 小鼠不易受到高剂量 VitD 饮食诱导的皮质骨丢失。需要进一步研究 WNT16 的生物学作用以及与 VitD 代谢对骨质量的相互作用，这可能为骨质疏松症的预后基因和预防曲线进展的潜在新靶点提供启示。
