Wnt16 protects chondrocytes from lumbar facet joint osteoarthritis through the Wnt/β-catenin pathway in low back pain patients
Wnt16 protects chondrocytes from lumbar facet joint osteoarthritis through the Wnt/β-catenin pathway in low back pain patients
复制标题
Wnt16 通过 Wnt/β-连环蛋白途径保护腰痛患者的软骨细胞免受腰椎小关节骨关节炎的影响。
DOI：
10.1080/08990220.2021.1977267
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发表时间：
2021-09-22
影响因子：
0.9
通讯作者：
Cui, Zhiming
中科院分区：
文献类型：
--
作者：
Wu, Chunshuai;Yu, Jinjuan;Cui, Zhiming
目的：腰背痛(LBP)是一种长期的、慢性的、无确切原因的症状。本研究试图在原有分级系统的基础上，结合病理结果和临床症状，提出一种新的分期系统，以更好地阐明小关节骨关节炎(FJOA)过程中与软骨退变相关的LBP的动态演变。目的：通过对软骨细胞的保护，为小关节相关性LBP的诊断、治疗和药物干预提供新的靶点。材料与方法：根据Weishaupt分级、CT和MRI新的退变分期方法，将所有小关节分为4组。采集腰椎间盘突出症患者行腰椎融合术后的小关节标本。通过分子生物学实验探讨WNT16对小关节退变的影响。Micro-CT检查和疼痛刺激试验检测WNT16在大鼠关节突关节软骨细胞中的生物学功能。结果：WNT16在III期和IV期小关节软骨细胞中明显增多和聚集，与软骨退行性变(OARSI)的病理结果一致。我们在体外发现Wnt16通过Wnt/β-catenin途径参与FJOA的调节，该途径可被特异性抑制剂Dkk1抑制。Wnt16表达丰富的大鼠对FJOA相关LBP表现出较高的缩足阈值和缩足潜伏期。大鼠腰椎Micro-CT检查显示WNT16对关节软骨细胞有保护作用。结论：本研究在原有关节软骨退变分级系统的基础上，结合病理结果和临床症状，提出了一种新的关节软骨退变分期系统。WNT16有望通过保护软骨细胞成为治疗FJOA的潜在靶点。
Purpose: Low back pain (LBP) is a long-lasting and chronic symptom without any exact cause. This study attempts to propose a new staging system based on the original grading system combined with pathological results and clinical symptoms to better clarify the dynamic evolution of LBP related to cartilage degeneration during facet joint osteoarthritis (FJOA). To explore a potential target for diagnosis, treatment, and drug intervention of facet joint osteoarthritis related LBP via protecting chondrocytes.Materials and methods: All the facet joints were divided into 4 groups according to our new degenerative staging system based on Weishaupt grade, CT and MRI. Collect the facet joint samples from patients whom suffered lumbar fusion surgery for lumbar disc herniation. Molecular biology experiments were used to explore the effect of Wnt16 on the degeneration of facet joints. Micro-CT examination and pain stimulation test checked the biological function of Wnt16 in rats.Results: Wnt16 was significantly increased and more aggregated in the facet joint chondrocytes in the Phase III and Phase IV, which is consistent with the pathological findings of cartilage degeneration (OARSI). We found that Wnt16 participated in the regulation of FJOA via Wnt/beta-catenin pathway in vitro, which was inhibited by specific inhibitor DKK1. The rats, rich expressed Wnt16, showed higher paw withdrawal thresholds and prolonged paw withdrawal latency to FJOA related LBP. Micro-CT examination for the lumbar spine of rats showed Wnt16 protected the chondrocytes from FJOA.Conclusions: This study defined a new staging system for LBP related cartilage degeneration of facet joint based on the original grading system combined with pathological results and clinical symptoms. Wnt16 is expected to be a potential target for treatment of FJOA via protecting chondrocytes.