Lessons from the proteomic study of osteoarthritis

Abstract

Osteoarthritis is the most common rheumatic pathology and one of the leading causes of disability worldwide. It is a very complex disease whose etiopathogenesis is not fully understood. Furthermore, there are serious limitations for its management, since it lacks specific and sensitive biomarkers for early diagnosis, prognosis and therapeutic monitoring. Proteomic approaches performed in the last few decades have contributed to the knowledge on the molecular mechanisms that participate in this pathology and they have also led to interesting panels of putative biomarker candidates. In the next few years, further efforts should be made for translating these findings into the clinical routines. It is expected that targeted proteomics strategies will be highly valuable for the verification and qualification of biomarkers of osteoarthritis.

Keywords:

• biomarkers
• cartilage
• chondrocytes
• joint
• osteoarthritis
• proteomics
• synoviocytes
• synovium

Acknowledgements

The authors would like to acknowledge the Rheumatology Division of the CHU A Coruña and the researchers of its Proteomics Group.

Financial & competing interests disclosure

This work is funded by grants from Fondo Investigación Sanitaria-Spain (PI11/02397, PI12/00329 and PI14/01707). C Ruiz-Romero is supported by the Miguel Servet program from Fondo Investigación Sanitaria-Spain (CP09/00114). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Osteoarthritis (OA) is a very complex pathology affecting joints, primarily characterized by articular cartilage degradation.

• Knowledge about the etiopathogenesis of OA is still limited, which hinders the development of efficient therapeutic strategies for its management.

• Proteomics has emerged in the last decade in the field of OA research for biomarker discovery and molecular characterization studies.

• In the area of OA, proteomic analyses performed either by two-dimensional electrophoresis, liquid chromatography coupled with mass spectrometry or protein arrays have been applied for the study of joint tissues, cells and their secretomes in order to increase knowledge about the molecular mechanisms involved in pathogenesis.

• Several proteomic analyses have been carried out on biological fluids and samples derived thereof for the search of novel, specific and sensitive protein biomarker candidates of OA.

• Differential shotgun proteomic studies using samples from diseased individuals and controls have led to the identification of several proteins associated with this disease.

• Further verification and validation studies are needed to translate proteomics findings into clinical practice for the management of OA.Targeted proteomics strategies appear as a valuable tool for the verification analyses of the best candidate biomarkers of OA. Development of these approaches on this field will enable the essential high-throughput and multiplexed evaluation of biomarker panels in large cohorts of patients and controls.