Endoplasmic reticulum stress-related protein GRP78 and CHOP levels in synovial fluid correlate with disease progression of primary knee osteoarthritis: A cross-sectional study.

BACKGROUND: Endoplasmic reticulum (ER) stress has been shown to play an important role in osteoarthritis (OA). OBJECTIVE: This study was aimed at assessing the relationship of endoplasmic reticulum (ER) stress-related glucose-regulated protein 78 (GRP78) and CCAAT/enhancer-binding protein homologous protein (CHOP) concentrations in the serum/synovial fluid (SF) with disease severity of primary knee osteoarthritis (pkOA). METHODS: Patients with pkOA together with healthy individuals were consecutively recruited from our hospital. The levels of GRP78 and CHOP in serum / SF were detected using enzyme-linked immunosorbent assay. The levels of IL-6 and MMP-3 were also examined. Radiographic progression of pkOA was evaluated based on Kellgren-Lawrence (K-L) grades. Receiver Operating Characteristic (ROC) curves were used to assess the diagnostic value of GRP78/CHOP levels with regard to K-L grades. The assessment of clinical severity was conducted using the visual analogue scale (VAS), Oxford knee score (OKS), and Lequesne algofunctional index (LAI). RESULTS: A total of 140 pkOA patients and 140 healthy individuals were included. Serum GRP78 and CHOP levels in pkOA patients were not significantly different from those in healthy individuals. The SF GRP78 and CHOP levels in healthy controls were not detected due to ethical reasons. Compared to those with K-L grade 2 and 3, the pkOA patients with K-L grade 4 had higher GRP78 and CHOP levels in the SF with statistical significance. In addition, the pkOA patients with K-L grade 3 exhibited drastically upregulated GRP78 and CHOP concentrations in the SF compared to those with K-L grade 2. Positive correlations of GRP78 and CHOP levels with K-L grades, IL-6, and MMP-3 levels in the SF were observed. ROC curve analysis indicated that both GRP78 and CHOP levels may act as decent indicators with regard to OA. GRP78 and CHOP concentrations in the SF were positively correlated with VAS/LAI score and negatively associated with OKS score. CONCLUSION: The study indicated that GRP78 and CHOP levels in the SF but not the serum were positively correlated with disease severity of pkOA.

Elevated Serum Levels of Monocyte Chemotactic Protein-1/Chemokine C-C Motif Ligand 2 are Linked to Disease Severity in Patients with Fibromyalgia Syndrome

Background: Elevated levels of monocyte chemotactic protein-1/chemokine C-C motif ligand 2 have been identified in fibromyalgia patients. Aims: To examine the potential association among serum levels of monocyte chemotactic protein-1/chemokine C-C motif ligand 2 with disease severity of fibromyalgia. Study Design: Cross-sectional study. Methods: Seventy-nine female patients with fibromyalgia and 75 healthy normal controls were included in our study. Serum levels of monocyte chemotactic protein-1/chemokine C-C motif ligand 2 were detected by enzyme-linked immune sorbent assays. The existence of tender points was evaluated based on the standardized manual tender point examination. Pressure pain thresholds at the knees, and bilateral trapezius muscles were measured with an algometer. A visual analog scale and the Revised Fibromyalgia Impact Questionnaire were utilized to assess the degree of pain and functional abilities. Results: Serum levels of monocyte chemotactic protein-1/chemokine C-C motif ligand 2 were significantly greater in patients with fibromyalgia compared with healthy controls (151.6±31.9 pg/mL vs 103.3±25.2 pg/mL, p<0.001). Patients with severe fibromyalgia had significantly higher serum levels of chemokine C-C motif ligand 2 than patients with mild and moderate fibromyalgia (173.1±21.9 pg/mL vs 151.0.0±35.1 pg/mL, p=0.01). Patients with moderate fibromyalgia revealed markedly augmented serum levels of chemokine C-C motif ligand 2 compared with patients with mild fibromyalgia (151.0±35.1 pg/mL vs 133.3±23.9 pg/mL, p=0.03). Serum levels of chemokine C-C motif ligand 2 were positively associated with tender point scores (r=0.455, p<0.001). In addition, serum levels of chemokine C-C motif ligand 2 were positively associated with pressure pain thresholds in both knees and bilateral trapezius muscles (knees: r=-0.349, p=0.002; trapezius muscles: r=-0.318, p=0.004). Finally, we found elevated serum levels of chemokine C-C motif ligand were also positively associated with the visual analog scale (r=0.368, p=0.001), and the Fibromyalgia Impact Questionnaire score (r=0.401, p<0.001). Conclusion: Elevated serum levels of monocyte chemotactic protein-1/chemokine C-C motif ligand 2 are linked to disease severity of fibromyalgia. Therapeutic interventions inhibiting monocyte chemotactic protein-1/chemokine C-C motif ligand 2 in fibromyalgia deserve additional studies.