Growth and differentiation factors for cartilage healing and repair.

Chondrocyte differentiation and the maintenance of function requires both transient and long-lasting control through humoral factors, particularly under stress, repair and regeneration in vivo or in vitro as in cell and tissue culture. To date, humoral factors from all major classes of molecules are known to contribute: ions (calcium), steroids (estrogens), terpenoids (retinoic acid), peptides (PTHRP, PTH, insulin, FGFs) and complex proteins (IGF-1, BMPs). They may act indirectly through membrane receptors and signal pathways or directly on transcriptional control elements. Those molecules may reach chondrocytes via free diffusion or may be bound to collagens or proteoglycans on extracellular matrix superstructures becoming available on metabolic processing of collagens and/or proteoglycans. Depending on their position in the metabolic cascade controlling chondrocyte development and homeostasis, they may be used in tissue engineering and regenerative approaches towards cartilage repair by direct application, carrier-mediated release or genetic delivery.