NKX3.2 plays a key role in regulating HIF1α-directed angiogenesis in chondrocytes

The cellular fraction of cartilage is mainly composed of one single cell type, the chondrocyte, which secretes, shapes and maintains the cartilaginous matrix that functions, in the case of epiphyseal cartilage, as the template for bone elongation. The biomechanical properties of cartilage are dependent mainly on the composition, as well as the macromolecular integrity of its matrix contributing to the functional and phenotypic differences between cartilage subtypes (1). For example, articular cartilage (AC) is a highly resilient tissue that allows low-friction joint articulation. In contrast, growth plate (GP) cartilage is populated by highly proliferative chondrocytes that undergo hypertrophic differentiation in an angiogenesis-promoting spatiotemporal manner, serving as a mold for longitudinal bone growth. As such, an in sharp contrast to AC, GP cartilage is a transient tissue and is replaced by bone in a process known as endochondral ossification (2).