engleski

Non-functional FAS ligand alters the pattern of new bone induction by BMP-2

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-specific markers – alkaline phosphatase, collagen, bone sialoprotein, osteocalcin, osteopontin, and bone morphogenetic proteins (BMP) -2, -4, and -7 ; and cytokines interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) 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 reflecting osteoblast transcription activity and lower level of bone sialoprotein and osteopontin that are involved in osteoblast maturation. Differences in the levels of expression of IL-1 and TNF-alpha were observed only at day 12 after rhBMP-2 implantation. These results suggest that gld mice have increased recruitment of cells of mesenchymal origin and an abnormal pattern of differentiation and maturation of the newly formed mesenchymal tissues, which may be due to their aberrant immune response.

bone; mice; immune system

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