Linear bone growth and maintenance of articular cartilage both require the proliferation and differentiation of chondrocytes. Much of the work done on chondrogenesis has focused on the role of the growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis. While it has long been known that nutrient deprivation impairs linear growth, this has widely been considered to be a function of indirect nutrient effects through modulation of the GH/IGF-I axis. However, our preliminary data indicate that the essential amino acid leucine can directly modulate chondrogenesis. Given that chondrocyte differentiation involves cellular hypertrophy, and that the recently characterized mTOR pathway regulates cell size in response to nutrient availability, we hypothesized that nutrient signaling via mTOR might exert direct effects on chondrocytes.This work has the potential to establish a role for nutrients in the indirect regulation of chondrogenesis via insulin and in direct regulation via the mTOR pathway.