Abstract
Symptomatic slow-acting drugs (SYSADOA) are increasingly used as effective therapies for osteoarthritis, representing an attractive alternative to analgesics or non-steroidal anti-inflammatory drugs to relieve disease symptoms. Pharmaceutical preparations of chondroitin sulfate, derived from animal sources, alone or in combination with glucosamine sulfate, are widely recognized for their beneficial effect on osteoarthritis treatment. A growing interest has also been devoted to understanding the molecular mechanisms modulated by SYSADOA using -omic strategies, most of which rely on chondrocytes as a model system. In this work, by using an integrated strategy based on unbiased proteomics and targeted cytokine profiling by a multiplexed protein array, we identified differences in the secretomes of human osteoarthritic synoviocytes in response to biotechnological unsulfated, and marine sulfated chondroitins treatments. The combined strategy allowed the identification of candidate proteins showing both common and distinct regulation responses to the two treatments of chondroitins. These molecules, mainly belonging to ECM proteins, enzymes, enzymatic inhibitors and cytokines, are potentially correlated to treatment outcomes. Overall, the present results provide an integrated overview of protein changes in human osteoarthritic synoviocytes secretome associated to different chondroitin treatments, thus improving current knowledge of the biochemical effects driven by these drugs potentially involved in pathways associated to osteoarthritis pathogenesis.
Highlights
Osteoarthritis (OA), a leading cause of disability in adult individuals, is a degenerative joint disease characterized by a multi-factorial etiology including obesity, aging and heredity
Since there is growing evidence that proteins released via vesicles including exosomes are used by cells for intercellular communication, we investigated if exosome-related proteins identified by enrichment analysis were predicted to be secreted using the SecretomeP/Signal P prediction algorithms
In addition to the cellular component enrichment analysis, we investigated if there was a correlation of responses to different chondroitin treatments by evaluating the gene ontology (GO) biological processes of differentially expressed proteins
Summary
Osteoarthritis (OA), a leading cause of disability in adult individuals, is a degenerative joint disease characterized by a multi-factorial etiology including obesity, aging and heredity. Current pharmacological treatments for OA are mainly symptom-focused and include combination therapies based on the analgesics or non-steroidal anti-inflammatory drugs (NSAIDs) administration and non-pharmacological methods (i.e., physical exercises and physiotherapy). Due to the numerous side effects deriving from the prolonged use of NSAIDs, chondroitin sulfate (CS) and glucosamine (GlcN) have been proposed as anti-osteoarthritis agents since 1990s. CS is a glycosaminoglycan made of 4)-β-GlcA-(1→3)-β-GalNAc-(1 disaccharide repeating units (GlcA = glucuronic acid, GalNAc = N-acetyl-galactosamine) with molecular weights (Mw), types and grades of sulfation related to animal tissues or age [3]. Highly purified pharmaceutical grade preparations of CS are included within the “symptomatic slow-acting drugs for osteoarthritis” (SySADOA) class [5,6]. SySADOA treatments have been recommended in the guidelines published by the Osteoarthritis Research Society International (OARSI) for the management of knee OA [7,8,9] and by the European League Against Rheumatism (EULAR) for the management of hip and knee OA [5,10,11]
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