Chitinase-3-like protein 1 plays a role in lumbar facet joint degeneration
10.3760/cma.j.cn121113-20211022-00616
- VernacularTitle:壳多糖酶3样蛋白质1在腰椎关节突关节退行性病变中的作用
- Author:
Yuanzhen CHEN
1
;
Lei WANG
;
Liangyu XIE
;
Shengnan CAO
;
Xiuchun YU
;
Huazhong LI
;
Weimin HUANG
;
Bin SHI
;
Dandan WANG
Author Information
1. 山东第一医科大学附属颈肩腰腿痛医院（山东省骨生物力学工程实验室）骨科，济南 250062
- Keywords:
Zygapophyseal joint;
Osteoarthritis;
Chondrocytes;
Chitinase-3-like protein 1
- From:
Chinese Journal of Orthopaedics
2022;42(17):1148-1155
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect of CHI3L1 on the biological function of chondrocytes and its role in lumbar facet joint degeneration.Methods:The human lumbar facet joint articular cartilage were collected, and the relative mRNA expression of CHI3L1 gene detected by quantitative fluorescence PCR. Then explored the correlation between joint degeneration and gender, age and relative mRNA expression of CHI3L1. Human chondrocytes were cultured in vitro. The effects of CHI3L1 on chondrocyte proliferation, cycling, and apoptosis, as well as expression of related inflammatory factors, were investigated. The mechanism by which CHI3L1 regulates the degeneration of articular cartilage was investigated using the signal transduction pathway protein chip.Results:There was a positive correlation between the grade of degeneration in lumbar facet joint and the relative expression of CHI3L1 gene mRNA ( r=0.76, P<0.001). There was no correlation with the patient's gender ( r=-0.12, P=0.500). A positive correlation between the age of patients and the relative expression of CHI3L1 gene mRNA was found ( r=0.47, P=0.005). Compared with the non-degenerative group, the expression of CHI3L1 gene mRNA significantly increased in the degenerative group, and the expression of CHI3L1 gradually increased with the aggravation in the grade of degeneration ( F=18.90, P<0.001). Compared with the non-degenerative group, the chondrocytes in the CHI3L1 group had significantly lower proliferation at 48 h (OD 490/fold=7.132), 72 h (OD 490/fold=4.803), 96 h (OD 490/fold=2.431) and 120 h (OD 490/fold=0.009). The ratio of chondrocytes in G1 phase, S phase and G2/M phase were 85.03%±3.05%, 12.78%±2.29% and 0.90%±0.76% in the CHI3L1 group, and 73.93%±2.73%, 22.81%±1.93% and 0.99%±0.87% in control group, respectively. There were significant differences in the percentage of chondrocytes in G1 phase ( t=4.70, P<0.001) and S phase ( t=5.80, P<0.001) between the two groups. The percentages of apoptosis in chondrocyte in CHI3L1 group and control group were 8.64%±0.76% and 5.68%±1.13%, which has a statistically difference ( t=4.47, P<0.001). The expression of IL-6 in chondrocytes of CHI3L1 group was 49.60±0.01 pg/ml, which was higher than that of 47.88±0.01 pg/ml in the control group ( t=132.70, P<0.001). The expression of TNF-α was 95.93±0.02 pg/ml, which was higher than 90.69±0.02 pg/ml in the control group ( t=376.10, P<0.001). There was significant difference in expression of IL-6 in chondrocytes between the CHI3L1 group and the control group ( t=132.72, P<0.001). The expression of TNF-α ( t=376.10, P<0.001) was statistically difference. Protein chip detected 53 proteins with significant differences in expression and 43 proteins with significant differences in protein phosphorylation levels. Bioinformatics analysis was used to identify 16 signaling pathways in which the above different proteins might be involved, including ErbB, PI3K, Akt, Ras, JAK, STAT3, MAPK pathway. In the MAPK pathway, the expression of MAPK1 and RAF1 proteins was higher in the chondrocytes of the CHI3L1 group than in the control group (1.094±0.00 vs. 0.814±0.00, 0.988±0.00 vs. 0.786±0.00; t=103.16, P<0.001; t=54.32, P<0.001). Compared with the control group, the expression of MAPK1 and RAF1 proteins was significantly increased in the chondrocytes of the CHI3L1 group. Conclusion:The expression of CHI3L1 is corrected to articular cartilage degeneration. CHI3L1 is able to inhibit the proliferation of articular chondrocytes, which regulated the cycling of chondrocytes from G1 phase to S phase, promote the apoptosis of chondrocytes, and promote the expression of IL-6 and TNF-α in chondrocytes. Regulation of chondrocytes biological function through the MAPK pathway, which is a potential biomarker for the clinical diagnosis and treatment of lumbar joint degeneration.
