Tackling chondrocyte hypertrophy with multifunctional nanoparticles

Osteoarthritis (OA) is the most common form of arthritis and leads to irreversible changes in all articular tissues and associated skeletal muscle.1,2 OA is a collection of different phenotypic sub-types involving different relative contributions of the stressors and pathogenic pathways that trigger and drive, respectively, disease development (Figure 1). Recent investigations have shown that OA is driven by interplay between local joint inammation (synovitis) and chondrocyte impaired bioenergy and protein homeostasis (see Liu-Bryan and Terkeltaub2 for an excellent review). Another important pathway being studied in the OA eld is that chondrocytes acquire a phenotype similar to terminal differentiating chondrocytes found at the growth plate and express markers of hypertrophic chondrocytes including type X collagen, matrix metalloproteinase-13 (MMP13) and vascular endothelial growth factor (VEGF).3 These ndings suggest that the loss of phenotypic stability of chondrocytes in OA reects an early futile process to repair stressed cartilage that ultimately leads to pathologic cartilage calcication.