Signalling molecules and growth factors for tissue engineering of cartilage-what can we learn from the growth plate?

Modern tissue engineering concepts integrate cells, scaffolds, signalling molecules and growth factors. For the purposes of regenerative medicine, fetal development is of great interest because it is widely accepted that regeneration recapitulates in part developmental processes. In tissue engineering of cartilage the growth plate of the long bone represents an interesting, well-organized developmental structure with a spatial distribution of chondrocytes in different proliferation and differentiation stages, embedded in a scaffold of extracellular matrix components. The proliferation and differentiation of these chondrocytes is regulated by various hormonal and paracrine factors. Thus, members of the TGFbeta superfamily, the parathyroid hormone-related peptide-Indian hedgehog loop and a number of transcription factors, such as Sox and Runx, are involved in the regulation of chondrocyte proliferation and differentiation. Furthermore, adhesion molecules, homeobox genes, metalloproteinases and prostaglandins play a role in the complex regulation mechanisms. The present paper summarizes the morphological organization of the growth plate and provides a short but not exhaustive overview of the regulation of growth plate development, giving interesting insights for tissue engineering of cartilage.