Chondroprotective Factors in Osteoarthritis: a Joint Affair

Abstract

Purpose of the review: Osteoarthritis is widely regarded as a spectrum of conditions that affect all joint tissues, typified by a common entity: cartilage loss. Here, we review recent progress and challenges in chondroprotection and discuss new strategies to prevent cartilage loss in osteoarthritis.

Recent findings: Advances in clinical, molecular, and cellular characterization are enabling improved stratification of osteoarthritis subtypes. Integration of next-generation sequencing and "omics" approaches with clinically relevant readouts shows promise in delineating both subtypes of disease and meaningful trial end points. Novel delivery strategies are enabling joint-specific delivery. Chondroprotection requires a whole joint approach, stratification of patient groups, and use of patient-relevant end points. Drug development should continue to explore new targets, while using modern technologies and recent knowledge to re-visit unsuccessful therapeutics from the past. The overarching goal for chondroprotection is to provide the right treatment(s) for the right patient at the right time.

Keywords: Chondroprotection; Drug development; Osteoarthritis; Stratification.

Fig. 1

A representation of an osteoarthritic knee, including the main contributing tissues and their interactions. The exact balance of tissue involvement and interaction is dependent on both joint site and the subtype of OA. Articular cartilage loss typifies OA but the exact balance of tissue involvement and interaction is dependent on joint site, stage and subtype of disease

Fig. 2

Overview of OA stratification categories and their interactions. Clinical signs and symptoms, risk factors, and molecular signatures interact and can define OA subtypes. The combinatorial effects of different stratification measures will define distinct subtypes and stages of OA. For example, risk factors such as trauma will drive changes in molecular and cellular signatures and altered clinical signs and symptoms. As OA progresses stratification categories will continue to feedback on each other, therefore individual stratification measures (or combinations thereof) may be specific to a particular stage of disease

Fig. 3

Integration of OA stratification categories with the translational cycle. The key stratification categories should be applied to studies of disease development and to pre-clinical and clinical drug development pathways. To refine critical stratification measures and identify relevant end points for pre-clinical and clinical studies, nextgeneration sequencing, “omics”, and cytometry approaches should be integrated with risk factors, clinical signs and symptoms. Tissue-based end points and stratification measures should be derived using well-phenotyped healthy and diseased tissues from the joint. Where appropriate, embedding tissue collection and analysis within enrolment and outcome stages of clinical trials would inform future studies across the translational cycle