Intraarticular injection of adipose mesenchymal stem cells over hyaluronic acid and collagen type II cleavage neoepitope in the treatment of osteoarthritis in dogs

Abstract

of cytokines such as IL-6. From the liver CRP is transported back to the inflamed tissue where it binds its receptors and thereby accumulated by the tissue. These fragments are released from the tissue as MMPs are upregulated in response to pro-inflammatory induction. C3M is a biomarker of type II collagen remodeling, which is released from the synovial membrane with induced with pro-inflammatory cytokines. The aim of the study was to investigate whether the level of the protein fingerprint CRPM together with the tissue turnover biomarker C3M could segregate OA patients with and without inflammatory arthritis. Methods: CRPM and C3M were measured in the serum of knee OA patients taking part of the two phase III RCTs (NCT00486434 and NCT00704847). Baseline and 2 year follow-up pain questionnaires and radiography were recorded for each patient. An array of additional biomarkers were measure; C1M, C2M, CTX-II, CTX-I and osteocalcin. The biomarkers were plotted against each other (figure) and cutoffs were set based on reference value and difference between clinical measures and biomarkers in the two patient groups were analyzed by Mann-Whitney. Results: Patients were separated into 2 groups; 1) patient with low CRPM and low C3M, and 2) patients with either high CRPM or high C3M, or with both high. 16% of the patients were found group 2. Several of the measures were higher in group 2: Cartilage degradation (C2M) and connective tissue degradation (C1M) were significantly higher (p¼0.0037, p<0.0001, respectively), as well as WOMAC subscale question Q5 (p¼0.0191). There was no group difference in KL score or JSW nor in CTX-I, CTX-II and osteocalcin. Group 1 patients (low in both CRPM and C3M) progressed structurally more group 1 patients (p¼0.046). Conclusions: We found that different of the two inflammatory markers could facilitate patient segregation. This may have many implications, however most importantly in the identification of more OA patients with the right diagnosis, inflammatory vs. non-inflammatory disease, which may benefit from a given treatment.