The future of deep phenotyping in osteoarthritis: How can high throughput omics technologies advance our understanding of the cellular and molecular taxonomy of the disease?

Abstract

Osteoarthritis (OA) is the most common form of musculoskeletal disease with significant healthcare costs and unmet needs in terms of early diagnosis and treatment. Many of the drugs that have been developed to treat OA failed in phase 2 and phase 3 clinical trials or produced inconclusive and ambiguous results. High throughput omics technologies are a powerful tool to better understand the mechanisms of the development of OA and other arthritic diseases. In this paper we outline the strategic reasons for increasingly applying deep phenotyping in OA for the benefit of gaining a better understanding of disease mechanisms and developing targeted treatments. This editorial is intended to launch a special themed issue of Osteoarthritis and Cartilage Open addressing the timely topic of "Advances in omics technologies for deep phenotyping in osteoarthritis". High throughput omics technologies are increasingly being applied in mechanistic studies of OA and other arthritic diseases. Applying multi-omics approaches in OA is a high priority and will allow us to gather new information on disease pathogenesis at the cellular level, and integrate data from diverse omics technology platforms to enable deep phenotyping. We anticipate that new knowledge in this area will allow us to harness the power of Big Data Analytics and resolve the extremely complex and overlapping clinical phenotypes into molecular endotypes, revealing new information about the cellular taxonomy of OA and "druggable pathways", thus facilitating future drug development.

Keywords: Cellular taxonomy; Deep phenotyping; Endotype; Osteoarthritis; Phenotype; Stratification.

Fig. 1

The cellular taxonomy of the synovial joint in health and disease. Many cell types are involved in the process of osteoarthritis development and progression but most of the research carried out to date has focused on articular chondrocytes. A more comprehensive cellular taxonomy should include all the cell types that are found within the synovial joint.

Fig. 2

Strategy of phenotyping and stratification of a heterogeneous population of osteoarthritis patients. Using this approach biological and high throughput multi-omics platforms may be used for patient stratification into different phenotypic categories that further refine the initial clinical classification criteria.