Non-functional Fas ligand increases the formation of cartilage early in the endochondral bone induction by rhBMP-2

Abstract It has previously been shown that mice with a defect in Fas ligand-mediated apoptosis have an enhancement of ectopic bone formation. We investigated the expression of bone-related markers - alkaline phosphatase, collagen, bone sialoprotein, osteocalcin, osteopontin, and bone morphogenetic proteins (BMP) -2, -4, and -7; and cytokines interleukin-1α (IL-1), IL-1β, and tumor necrosis factor-α (TNF-α) in ectopic new bone induced by recombinant human (rh) BMP-2 in mice without functional Fas-ligand ( gld mice). At day 6 after rhBMP-2 implantation, gld mice formed more cartilage and mesenchyme compared with their wild type littermates. At later stages, gld mice did not differ from the control mice in the volume of newly formed tissue, expressing higher level of BMP genes and lower levels of genes involved in osteoblast maturation - bone sialoprotein and osteopontin. Differences in the levels of expression of IL-1α and TNF-α were observed only at day 12 after rhBMP-2 implantation. These results suggest that gld mice have an increased recruitment of cells of mesenchymal origin and an abnormal pattern of differentiation and maturation of the newly formed mesenchymal tissues.