Chemical Biology: Approaches to Drug Discovery and Development to Targeting Disease

Chapter 15: Osteoarthritis

Marjolaine Gosset

Jérémie Sellam

Claire Jacques

Francis Berenbaum

Paris Universitas, Paris, France

Paris Universitas APHP Saint-Antoine Hospital, Paris, France

Osteoarthritis (OA) is considered the most common skeletal disorder and is characterized by cartilage degradation and osteophyte formation in joints. Although it is the most common joint disease, OA is often difficult to define because it is heterogeneous in its presentation style, rate of progression, and manifestations. Recently, new insights into the molecular biological basis of chondrocyte differentiation and cartilage homeostasis have been reported. The pathology of osteoarthritis is now interpreted as the disruption of balance between anabolic and catabolic signals. This chapter focuses on the risk factors, cellular and molecular mechanisms involved in OA, tools to study OA such as animal models and biomarkers, as well as treatment. Findings with regard to the physiologic and pathologic mechanisms involved in OA have made it possible to target therapeutic approaches more accurately, which allows the development of new drugs to reduce or block the progression of the disease.

15.1 Biological and Biophysical Background of Osteoarthritis

15.1.1 Diagnosis

OA is the most common chronic joint disorder. The most frequently affected sites are the hands, knees, hips, and spine [1] (Fig. 15.1). It results from degeneration of a synovial joint, which leads to a generally progressive loss of articular ...