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Multiple hereditary exostoses is an autosomal dominant inherited disease causing exostoses: growth on the bones of children. The disease is mainly caused by mutated exostosin (EXT)-1 or EXT-2 genes. These mutations yield non-functional EXT-gene products. Lack of functional proteins cause a defect in heparan sulphate synthesis and therefore in proteoglycan modification and cell signalling. It is assumed that a subset of chondrocytes form an exostoses, through a growth and differentiation process which is only partially understood. The place of origin of these exostoses-forming chondrocytes is still unknown. We also do not know in detail which processes influence the exostoses growth, and what shelters the exostoses from being resorbed by osteoclast activity. In this paper we systematically review the major pathophysiological theories of exostoses, with a focus on the aforementioned knowledge gaps.

Cartilage, due to its unique physiology (lack of vasculature), can be potentially repaired using tissue engineered in the laboratory, by combining cells and with a supporting scaffold. This requires a marriage between material science, cell biology, and translational medicine, a concept well established as Tissue Engineering. Over the years the in vivo and in vitro chondrogenic potential of periosteum has been recognised by many researchers and as such periosteum is explored both to repair cartilage defects directly by transplanting periosteum into the cartilage defect or by using periosteum as a cell source for cartilage engineering purposes. The initial example hereof is the first generation of Autologous Chondrocyte Transplantation. Graft hypertrophy and ossification remain the primary drawbacks of cartilage repair strategies using engineered cartilage. These drawbacks may (partially) be due to the endochondral ossification process that can take over when cartilage is repaired. In this process chondrogenesis of progenitor cells is followed by hypertrophy of these cells and subsequent ossification. Periosteal progenitor cells go through this process in order to heal bone fractures. This review provides an overview of the role of periosteum in cartilage repair and cartilage tissue engineering and illustrates how periosteum can be used as a model to study the endochondral process. Such studies may provide clues to further optimize cartilage tissue engineering by identifying important factors which are capable of maintaining cells in their chondrogenic phenotype. Finally, the use of periosteum to engineer cartilage in vivo at an extra-articular site is described.