J Appl Biomed 22:40-48, 2024 | DOI: 10.32725/jab.2024.001

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

Dan-Dan Liu¹ a, Yuan-Chuang Zhao² a, Hai-Hong Li¹, Lian-Jun Yin¹, Jun-Qi Chen¹ *, Gang Liu^{3, *}

¹ Southern Medical University, The Third Affiliated Hospital, Department of Rehabilitation, 510630 Guangzhou, Guangdong Province, China

² Guangzhou Special Service Recuperation Center of PLA Rocket Force, The Fourth Recuperate Area, Department of Rehabilitation, 510515 Guangzhou, Guangdong Province, China

³ Southern Medical University, Nanfang Hospital, Department of Rehabilitation Medicine, 510515 Guangzhou, Guangdong Province, China

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.

Keywords: CCAAT, enhancer-binding protein homologous protein; Disease severity; Glucose-regulated protein 78; Knee osteoarthritis

Conflicts of interest:

The authors have no conflict of interest to declare.

Received: July 11, 2023; Revised: December 7, 2023; Accepted: January 18, 2024; Prepublished online: January 19, 2024; Published: March 15, 2024  Show citation