Effects of Human BMP-2 on Trans-Differentiation of Myoblast Cells and Human Rhabdomyosarcoma Using an In Vitro Model System

Fibrodysplasia Ossificans Progressiva (FOP) is an autosomal dominant disease that affects one in every two million persons. It is a disease that stimulates ossification in injured muscle cells. This mutation affects the bone morphogenetic protein receptor (BMPR), which is found on the surface of skeletal muscle cells. When bone morphogenetic proteins (BMP) come into contact with these receptors it causes a cascade of events to occur that transform skeletal muscle cells into bone cells. This mutation causes these receptors to remain constitutively activated in the presence of BMP. We compared the effects of human BMP2 on mouse myoblast cells (C2C12) and rhabdomyosarcoma (RD; human muscle cancer) cells. RD cells were used as the human muscle model for the BMPR. The results confirmed that C2C12 cells increased alkaline phosphatase (ALT) levels when BMP2 was added. ALT is one of the precursors for bone growth. The RD cells unexpected displayed relatively high ALT levels without the presence of BMP2. These results demonstrate trans-differentiation in C2C12 and RD cells, confirming that myoblast cells were reprogrammed to osteoblast cells by the addition of BMP2. Trans-differentiation is being initiated by the inflammatory response and molecules that are being delivered to these injured muscle cells. This experiment was preliminary work to find specific molecules that are coupling with BMP to transform injured myoblast cells into osteoblast cells