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

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. 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. 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. 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.

下腰痛（Low back pain, LBP）是一类病因不明的长期慢性症状。本研究旨在结合原始分级系统、病理结果与临床症状，提出全新的分期体系，以更清晰地阐明与关节突关节骨关节炎（facet joint osteoarthritis, FJOA）相关的LBP患者软骨退变的动态演变过程；同时通过保护软骨细胞，为FJOA相关LBP的诊断、治疗及药物干预探索潜在靶点。所有关节突关节样本均基于我们结合魏绍普特分级（Weishaupt grade）、CT及MRI建立的全新退变分期体系，被分为4组。我们从因腰椎间盘突出症接受腰椎融合术的患者体内收集关节突关节样本。采用分子生物学实验探究Wnt16对关节突关节退变的影响；通过Micro-CT检查与疼痛刺激试验，检测Wnt16在大鼠体内的生物学功能。研究发现，Wnt16在Ⅲ期与Ⅳ期患者的关节突关节软骨细胞中显著升高且聚集，这与软骨退变的病理表现（OARSI）一致。我们证实，体外实验中Wnt16通过Wnt/β-连环蛋白通路参与调控FJOA的发生发展，且该作用可被特异性抑制剂DKK1抑制。高表达Wnt16的大鼠，其针对FJOA相关LBP的缩爪阈值更高、缩爪潜伏期更长；对大鼠腰椎的Micro-CT检查显示，Wnt16可保护软骨细胞免受FJOA的侵害。本研究基于原始分级系统，结合病理结果与临床症状，建立了针对FJOA相关LBP软骨退变的全新分期体系。Wnt16有望成为通过保护软骨细胞治疗FJOA的潜在靶点。