Key insights and implications of cartilage degradation in osteoarthritis.

BACKGROUND

Progressive degradation of articular cartilage is characteristic of osteoarthritis (OA), but OA is more than a wear-and-tear disease of the cartilage.

SIGNIFICANT DISCOVERIES

It is a complex, multifactorial disease affecting all joint tissues, amplified by local and systemic inflammation. Chondrocytes play a crucial role in cartilage homeostasis and various molecular pathways that leading to their catabolic state have been identified. Cartilage degradation fragments and direct exposure of chondrocytes to extracellular matrix molecules provide feedback loops that further stimulate the catabolic profile. Synovial inflammation and subchondral bone changes enhance cartilage degradation by changing the joint environment, secreting pro-inflammatory cytokines and proteolytic enzymes, and attracting immune cells. The heterogeneity of the disease is underscored by the recognition on various phenotypes and endotypes, although consensus on classification of subtypes is lacking.

LESSONS LEARNED

In the last 25 years, we have learned that timely treatment of joint injuries and repairing the meniscus are the best options to delay cartilage degradation and the development of post-traumatic OA. In addition, clinical studies have shown that cartilage thickness can be restored, but it does not necessarily provide clinical improvements.

KNOWLEDGE GAPS AND BARRIERS

So far, there is no disease modifying OA drug (DMOAD) available. The development of DMOADs is partially hindered by the requirement of long preclinical and clinical studies, as cartilage degradation is a slow process. Availability of biomarkers as surrogate endpoint could accelerate the development. Biomarker panels for early diagnosis and patient stratification could also advance the field.

OUTLOOK

Currently emerging treatment approaches, such as using regenerative medicine, promising for successful treatment.