Pharma-grade extractive
chondroitin sulfate (CS) is widely used for
osteoarthritis (OA) treatment. Recently, unsulfated biofermentative
chondroitin (BC) proved positive effects in OA in vitro model. This study, based on primary pathological human synoviocytes, aimed to analyze, by a multiplex assay, a panel of OA-related
biomarkers in response to short-term treatments with bovine (CSb), pig (CSp) and fish (CSf) chondroitins, in comparison to BC. As expected, all samples had anti-inflammatory properties, however CSb, CSf and especially BC affected more
cytokines and
chemokines. Based on these results and molecular weight similarity, CSf and BC were selected to further explore the synoviocytes' response. In fact, Western blot analyses showed CSf and BC were comparable, downregulating OA-related
biomarkers such as the
proteins mTOR,
NF-kB, PTX-3 and COMP-2. Proteomic analyses, performed by applying a nano-LC-MS/MS TMT isobaric labelling-based approach, displayed the modulation of both common and distinct molecules to
chondroitin treatments. Thus, CSf and BC modulated the
biological mediators involved in the
inflammation cascade, matrix degradation/remodeling,
glycosaminoglycans' synthesis and cellular homeostasis. This study helps in shedding light on different molecular mechanisms related to OA disease that may be potentially affected not only by animal-source
chondroitin sulfate but also by unsulfated biofermentative
chondroitin.