Chondrocyte activity is increased in psoriatic arthritis and axial spondyloarthritis

Abstract

BackgroundPsoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) are chronic inflammatory rheumatic diseases with complex origins. Both are characterized by altered extracellular matrix remodeling in joints and entheses that results in destructive and osteochondral proliferative lesions. There is a need for biomarkers reflecting core disease pathways for diagnosis and disease mapping. Pro-C2 reflects mature cartilage collagen type IIB formation, while C-Col10 represents turnover of type X collagen, which is exclusively expressed by hypertrophic chondrocytes. The objectives of this study were to study cartilage metabolism in axSpA and PsA by assessing Pro-C2 and C-Col10 and to evaluate their diagnostic utility against a healthy reference population.MethodsPatients with PsA (n = 101) or axSpA (n = 110) were recruited consecutively from three rheumatology outpatient clinics. Demographic and clinical disease measures were recorded. Pro-C2 and C-Col10 were quantified in serum by using newly developed and specific competitive enzyme-linked immunosorbent assays based on monoclonal antibodies. One-way analysis of variance and Tukey’s multiple comparison tests were performed on log-transformed data. ROC curve analysis was carried out to evaluate their discriminative power.ResultsPro-C2 levels in serum were significantly increased in both axSpA (median concentration 1.11 ng/ml, 0.67–1.64) and PsA (median concentration 1.03 ng/ml, 0.53–1.47) compared with healthy controls (median concentration 0.30 ng/ml, 0.16–0.41) (p < 0.0001). Pro-C2 did not differ according to treatment. C-Col10 was slightly but equally elevated in the PsA and axSpA groups vs. the control group, but it was significantly lower in patients with axSpA undergoing tumor necrosis factor-α inhibitor (TNFi) treatment. ROC curve analysis revealed AUCs of 0.85 (95 % CI 0.79–0.89) for axSpA and 0.81 (95 % CI 0.75–0.86) for PsA.ConclusionsThese findings indicate that cartilage collagen metabolism was enhanced in the axSpA and PsA groups compared with the healthy control group. The lower C-Col10 level in patients with axSpA undergoing TNFi treatment may reflect that hypertrophic chondrocytes in axSpA are targeted by TNFi. ROC curve analysis showed a diagnostic potential for Pro-C2 in axSpA and PsA.

RNAseq-Based Prioritization Revealed COL6A5, COL8A1, COL10A1 and MIR146A as Common and Differential Susceptibility Biomarkers for Psoriasis and Psoriatic Arthritis: Confirmation from Genotyping Analysis of 1417 Italian Subjects

“…This result supports the potential implication of bone and cartilage metabolism-related processes in the onset and progression of PsA [20]. Accordingly, it has been found that Collagen X metabolism was enhanced in patients affected by PsA and Axial Spondyloarthritis [21]. This evidence supports COL10A1 as a contributor to the rheumatological features observed in PsA.…”

Potential diagnostic value of a type X collagen neo-epitope biomarker for knee osteoarthritis

“…Although type X collagen is exclusively expressed by hypertrophic chondrocytes in cartilage, it has been found in human lumbar intervertebral discs 38,39 . We previously reported that C-Col10, an assay measuring the C-terminus of type X collagen, was significantly higher in spondyloarthritis (SpA) patients due to the syndesmophyte outgrowth similar to osteophyte formation in OA 40 . Thus, the origin of serological Col10neo is worthy of further investigation.…”

The minor collagens in articular cartilage

“…Type X collagen is subject to interstitial collagenase and gelatinase cleavage at two distinct sites within triple helix domain (Goldring et al, 2013 ). He et al reported that C-Col 10, which is a C-terminal fragment of the NC1 domain in type X collagen, significantly elevated in OA patients compared to healthy subjects (He et al, 2014 ; Gudmann et al, 2016 ). Type XI collagen is resistant to collagenase but hydrolysed by gelatinases resulting in a number of degradation products.…”