U T Timur1, H Jahr2, J Anderson3, D C Green3, P J Emans4, A Smagul3, L W van Rhijn4, M J Peffers3, T J M Welting5. 1. Laboratory for Experimental Orthopedics, Department of Orthopedic Surgery, Maastricht University, Universiteitssingel 50, 6229 ER, Maastricht, the Netherlands; Department of Orthopedic Surgery, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ, Maastricht, the Netherlands. 2. Department of Anatomy and Cell Biology, RWTH Aachen University, Wendlingweg 2, 52074 Aachen, Germany; Department of Orthopedic Surgery, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ, Maastricht, the Netherlands. 3. Institute of Life Course and Medical Sciences, Faculty of Health and Life Sciences, University of Liverpool, Liverpool L69 3BX, United Kingdom. 4. Department of Orthopedic Surgery, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ, Maastricht, the Netherlands. 5. Laboratory for Experimental Orthopedics, Department of Orthopedic Surgery, Maastricht University, Universiteitssingel 50, 6229 ER, Maastricht, the Netherlands; Department of Orthopedic Surgery, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ, Maastricht, the Netherlands. Electronic address: t.welting@maastrichtuniversity.nl.
Abstract
OBJECTIVE: 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. DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.
OBJECTIVE: 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. DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Guus G H van den Akker; Marjolein M J Caron; Mandy J Peffers; Tim J M Welting Journal: Curr Opin Rheumatol Date: 2022-01-01 Impact factor: 5.006
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