Osteoclast formation in fibrodysplasia ossificans progressiva: The use of periodontal ligament fibroblasts in rare bone disease research

Fibrodysplasia Ossificans Progressiva (FOP) is a very rare genetic disease characterized by heterotopic ossification (HO). Removal of the extra formed bone is rarely performed since this often results in new and increased HO at the site of removal. Therefore, alternative sources of cells that can answer mechanistic aspects of FOP are required. In this thesis we investigated osteoclast formation in FOP and the influence of Activin-A on this process. FOP patient derived periodontal ligament fibroblasts were used to investigate their osteogenic - and osteoclast inducing capacity and monocytes isolated from FOP patient derived blood samples were used as osteoclast precursors. This thesis shows that periodontal ligament fibroblasts are very useful for research on rare bone diseases such as FOP. It provides us with a relatively easy available model for studying osteogenesis (bone production) and osteoclast formation (bone resorption). In addition, the described studies show that the mutation that causes FOP does not have a significant influence on the formation of osteoclasts. Even in the presence of Activin-A, there is hardly any difference in effect between control and FOP cells, suggesting that the osteoclasts do not play a major role in the formation of the heterotopic bone in FOP. However, it appears that Activin-A has a large positive influence on the size of the osteoclast, independent of the presence of the FOP-causing mutation. Understanding the effect of Activin-A on osteoclast formation in general may be important in disease states where this molecule has an important role in disease development, such as in FOP