Abstract
For many proteins from osteoarthritic synovial fluid, their intra-articular tissue of origin remains unknown. In this study we performed comparative proteomics to identify osteoarthritis-specific and joint tissue-dependent secreted proteins that may serve as candidates for osteoarthritis biomarker development on a tissue-specific basis. Protein secretomes of cartilage, synovium, Hoffa's fat pad and meniscus from knee osteoarthritis patients were determined using liquid chromatography tandem mass spectrometry, followed by label-free quantification. Validation of tissue-dependent protein species was conducted by ELISA on independent samples. Differential proteomes of osteoarthritic and non-osteoarthritic knee synovial fluids were obtained via similar proteomics approach, followed by ELISA validation. Proteomics revealed 64 proteins highly secreted from cartilage, 94 from synovium, 37 from Hoffa's fat pad and 21 from meniscus. Proteomic analyses of osteoarthritic vs non-osteoarthritic knee synovial fluid revealed 70 proteins with a relatively higher abundance and 264 proteins with a relatively lower abundance in osteoarthritic synovial fluid. Of the 70 higher abundance proteins, 23 were amongst the most highly expressed in the secretomes of a specific intra-articular tissue measured. Tissue-dependent release was validated for SLPI, C8, CLU, FN1, RARRES2, MATN3, MMP3 and TNC. Abundance in synovial fluid of tissue-dependent proteins was validated for IGF2, AHSG, FN1, CFB, KNG and C8. We identified proteins with a tissue-dependent release from intra-articular human knee OA tissues. A number of these proteins also had an osteoarthritis-specific abundance in knee synovial fluid. These proteins may serve as novel candidates for osteoarthritis biomarker development on a tissue-specific basis.
Highlights
Knee osteoarthritis (OA) is an increasingly prevalent disabling condition with serious socioeconomic impact on a global scale[1,2]
In the search of diagnostic targets that are capable of identifying biomolecular changes in knee joint homeostasis, efforts have been made to understand the biomolecular composition of synovial fluid and to identify OA-related changes in its composition
In the search of diagnostic targets that are capable of identifying biomolecular changes in knee joint homeostasis, important efforts have been made to understand the proteomic composition of synovial fluid and to identify OA-related changes in its composition10,19,27e29
Summary
Knee osteoarthritis (OA) is an increasingly prevalent disabling condition with serious socioeconomic impact on a global scale[1,2]. No effective treatment exists to attenuate OA progression, and the current standard of care involves conservative painkilling drug therapies, physiotherapy and visco-supplementation of the affected joint. These therapies are all aimed at postponing total joint arthroplasty, which is an invasive surgical approach to alleviate the patient's OA-related pain and regain mobility when the condition reaches end-stage. Knee OA is currently diagnosed radiographically by significant joint space narrowing, osteophyte formation and subchondral bone lesioning[3] These macroscopic changes are indicative of the disease progressing towards its end-stage, and often the patient presents with symptoms such as pain, joint stiffness and debilitating mobility limitations prior to diagnosis[4]. Since the synovial fluid is in contact with many of the important intra-articular tissues, it represents a promising body fluid for developing OA biomolecular diagnostics to access the condition of the joint as whole, as well as with a potential for joint tissue-specific diagnostics[9,10]
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