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Cartilage tissue protects the ends of long bones and forms a structural component of body parts such as the rib cage, nose, and intervertebral discs. Cartilage tissue contains cells known as chondrocytes that produce large amounts of a collagenous extracellular matrix rich in proteoglycans, with the three distinct types of cartilage—elastic cartilage, hyaline cartilage, and fibrocartilage—differing with regard to the relative amounts of collagen and proteoglycan. As the articular cartilage of joints displays only a limited capacity for repair, the gradual thinning and subsequent loss of cartilage tissue between bones or cartilage damage due to trauma can prompt the onset of osteoarthritis, a painful disorder that significantly impedes motion. Therapeutic approaches for osteoarthritis with promising clinical results include the implantation of autologous chondrocytes1 or allogeneic cartilage2; however, the small number of isolated chondrocytes and the general scarcity of cartilage donors represent significant obstacles to these approaches. Given their virtually unlimited expansion and differentiation potential, the directed differentiation of induced pluripotent stem cells (iPSCs) represents an exciting means to model cartilage development and disease and create new tissue to treat articular cartilage damage.3,4 Current research aims in this field include deciphering the molecular mechanisms controlling iPSC chondrogenesis and optimizing differentiation protocols toward their hoped-for clinical application. In the first of our Featured Articles published this month in STEM CELLS, Willard et al. describe the importance of the osmo- and mechano-sensitive cation channel transient receptor potential vanilloid 4 (TRPV4) to the chondrogenic differentiation of murine iPSCs.5 In a Related Article published recently in STEM CELLS Translational Medicine, Yamashita et al. explored the impact of culture substrates on the chondrogenic differentiation of human iPSCs and established how the inactivation of the yes-associated protein (YAP) improved cartilage formation.6

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