ESPE Yearbook of Paediatric Endocrinology

In brief. This basic research study used an in vitro method to recapitulate key steps in growth plate development and endochondral bone formation, using induced pluripotent stem cells (iPSCs). This method provides original material that can be used to study growth plate and bone development, to assess the consequences of genetic variants involved in bone diseases, and to test new therapies.

Commentary: In vertebrates, the longitudinal growth of long bones is determined through endochondral ossification at the growth plate level. During this process, chondrocytes, which are derived from the condensation of undifferentiated mesenchymal cells, undergo a series of proliferation and differentiation steps. First, small chondrocytes rapidly divide and form columns in the proliferating zone. Then, in the pre- and early-hypertrophic zone, chondrocytes undergo hypertrophic differentiation, characterised by increased cell size and the synthesis of collagen type 10, which is then calcified by enzymes such as alkaline phosphatase. In the late hypertrophic zone, terminally differentiated chondrocytes undergo apoptosis, and the cartilaginous calcified matrix is degraded, through the simultaneous action of matrix metalloproteinase and the invasion of blood vessels, along with osteoclasts, and replaced by bone.

These authors report an in vitro method that recapitulates the various proliferation and differentiation steps of endochondral bone formation. Using induced pluripotent stem cells (iPSCs), this method allows the generation of cartilage organoids that can be directed towards an articular phenotype or a growth plate phenotype that matures to hypertrophy. The hypertrophic chondrocytes of the growth plate can in turn be differentiated into osteoblasts that synthesise the bone-specific extracellular matrix and mineralise this matrix. A detailed analysis of the gene expression profile during the different stages of proliferation and differentiation is provided.

This method provides original material for studying growth plate and bone development, assessing the consequences of genetic variants involved in bone diseases and testing new therapies.