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在腰痛患者中,Wnt16通过Wnt/β-连环蛋白途径保护软骨细胞免受腰椎小关节骨关节炎的侵害。

Wnt16 protects chondrocytes from lumbar facet joint osteoarthritis through the Wnt/β-catenin pathway in low back pain patients.

作者信息

Wu Chunshuai, Yu Jinjuan, Xu Guanhua, Bao Guofeng, Zhang Jinlong, Xue Pengfei, Jiang Jiawei, Chen Jiajia, Chen Chu, Hong Hongxiang, Cui Zhiming

机构信息

Department of Spine Surgery, Affiliated Hospital 2 of Nantong University, Nantong University, The First People's Hospital of Nantong, Nantong, PR China.

Outpatient Department, The Third People's Hospital of Nantong, Nantong, PR China.

出版信息

Somatosens Mot Res. 2021 Dec;38(4):339-346. doi: 10.1080/08990220.2021.1977267. Epub 2021 Sep 23.

Abstract

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/β-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.

摘要

目的

下腰痛(LBP)是一种持续存在的慢性症状,病因尚不明确。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)期间与软骨退变相关的下腰痛的动态演变。通过保护软骨细胞,探索小关节骨关节炎相关下腰痛的诊断、治疗和药物干预的潜在靶点。

材料与方法

根据基于Weishaupt分级、CT和MRI的新退变分期系统,将所有小关节分为4组。收集因腰椎间盘突出症接受腰椎融合手术患者的小关节样本。采用分子生物学实验探讨Wnt16对小关节退变的影响。通过显微CT检查和疼痛刺激试验检测Wnt16在大鼠体内的生物学功能。

结果

Wnt16在III期和IV期小关节软骨细胞中显著增加且聚集更多,这与软骨退变的病理表现(OARSI)一致。我们发现Wnt16在体外通过Wnt/β-连环蛋白途径参与FJOA的调节,特异性抑制剂DKK1可抑制该途径。富含Wnt16的大鼠对FJOA相关下腰痛表现出更高的爪部撤离阈值和更长的爪部撤离潜伏期。对大鼠腰椎的显微CT检查显示Wnt16可保护软骨细胞免受FJOA影响。

结论

本研究基于原有分级系统,结合病理结果和临床症状,定义了一种与小关节软骨退变相关的下腰痛新分期系统。Wnt16有望通过保护软骨细胞成为治疗FJOA的潜在靶点。

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