Ultramicroscopic Aspects of the Conversion of Fibroblasts to Chondrocytes in the Mouse Dorsal Subfascia Induced by Bone Morphogenetic Protein (BMP)

Direct conversion of typical fibroblasts to chondrocytes in the mouse fibrous connective tissue induced by bone morphogenetic protein (BMP) was observed by light as well as electron microscopy. A pellet containing BMP obtained from a murine osteosarcoma was transplanted into the dorsal subfascia of 5 week-old mice. Until 3 days after implantation of BMP, all the connective tissue cells in the pellet region of the dorsal subfascia showed the fine structural features of typical fibroblasts. The cells in the pellet region changed their shape from spindle-like to polygonal by 5 days after implantation. At this time, small vacuoles 150-450nm and vesicles 40-60nm in diameter, containing a homogeneous substance of low electron density, appeared in the cytoplasm of the cells. A small amount of extracellular substance, showing metachromasia by toluidine blue staining, was seen around the cells. Moreover, autoradiography of 35S revealed the uptake of sulfur by the cells and its accumulation in the extracellular substance around the cells in the pellet region at 5 days. The rough endoplasmic reticulum and Golgi apparatus increasingly developed with time and after 7 days both elements were distributed throughout the cytoplasm. The cytoplasmic small vacuoles and vesicles also increased in number with time, and the metachromatic extracellular substance containing fine filamentous meshwork and many tiny particles, which was regarded as the matrix of cartilage, also increased rapidly in amount. By 9 days, the cells in the pellet region became oval or round in shape, showing many short cytoplasmic processes. This finding indicates that the fibroblasts in the BMP pellet region transform to chondroblasts at least by 5 days after implantation, and become typical chondrocytes by 9 days.