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

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.

Keywords:

• Low back pain
• lumbar facet joint osteoarthritis
• chondrocytes
• Wnt/β-catenin pathway

Disclosure statement

All the authors declare no conflict of interest.

Additional information

Funding

This study was supported by National Natural Science Foundation of China [grant numbers: 81771319], Nantong Health and Family Planning Commission Research Project [grant numbers: WKZL2018001], Six Talent Peak Projects in Jiangsu Province [grant numbers: 2017-WSW-156], Nantong Science and Technology Plan Project [grant numbers: JC2019070, JC2020013], Medical research project of Jiangsu Commission of Health [grant numbers: ZDB2020004], Young Medical Talents Project of Jiangsu Province [grant numbers: QNRC2016413], and Nantong Social People's Livelihood Technology Project [grant numbers: MS12019027].