Proteomic profiling and functional characterization of early and late shoulder osteoarthritis
- Equal contributors
1 Department of Orthopaedics, Case Western Reserve University, School of Medicine, Cleveland, OH, USA
2 Centre de Recherche en Rhumatologie et Immunologie, Centre de Recherche du Centre Hospitalier Universitaire de Québec, Faculté de Médecine de l’Université Laval, Québec, QC G1V 4G2, Canada
3 Laboratory for Integrated Bioinformatics, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), RIKEN Yokohama Institute, Kanagawa, 230 0045, Japan
4 Case Center for Proteomics and Bioinformatics, Case Western Reserve University, School of Medicine, Cleveland, OH, USA
5 Cleveland Shoulder Institute, University Hospitals of Cleveland, 5885 Landerbrook Drive, Monarch Center, Mayfield Heights, OH, 44121, USA
Arthritis Research & Therapy 2013, 15:R180 doi:10.1186/ar4369Published: 6 November 2013
The development of effective treatments for osteoarthritis (OA) has been hampered by a poor understanding of OA at the cellular and molecular levels. Emerging as a disease of the 'whole joint’, the importance of the biochemical contribution of various tissues, including synovium, bone and articular cartilage, has become increasingly significant. Bathing the entire joint structure, the proteomic analysis of synovial fluid (SF) from osteoarthritic shoulders offers a valuable 'snapshot’ of the biologic environment throughout disease progression. The purpose of this study was to identify differentially expressed proteins in early and late shoulder osteoarthritic SF in comparison to healthy SF.
A quantitative 18O labeling proteomic approach was employed to identify the dysregulated SF proteins in early (n = 5) and late (n = 4) OA patients compared to control individuals (n = 5). In addition, ELISA was used to quantify six pro-inflammatory and two anti-inflammatory cytokines.
Key results include a greater relative abundance of proteins related to the complement system and the extracellular matrix in SF from both early and late OA. Pathway analyses suggests dysregulation of the acute phase response, liver x receptor/retinoid x receptor (LXR/RXR), complement system and coagulation pathways in both early and late OA. The network related to lipid metabolism was down-regulated in both early and late OA. Inflammatory cytokines including interleukin (IL) 6, IL 8 and IL 18 were up-regulated in early and late OA.
The results suggest a dysregulation of wound repair pathways in shoulder OA contributing to the presence of a 'chronic wound’ that progresses irreversibly from early to later stages of OA. Protease inhibitors were downregulated in late OA suggesting uncontrolled proteolytic activity occurring in late OA. These results contribute to the theory that protease inhibitors represent promising therapeutic agents which could limit proteolytic activity that ultimately leads to cartilage destruction.