Non-functional Fas ligand increases the formation of cartilage early in the endochondral bone induction by rhBMP-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-related markers - alkaline phosphatase, collagen, bone sialoprotein, osteocalcin, osteopontin, and bone morphogenetic proteins (...
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Published in: | Life sciences (1973) Vol. 74; no. 1; pp. 13 - 28 |
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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. |
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AbstractList | 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-1alpha (IL-1), IL-1beta, 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 and lower levels of genes involved in osteoblast maturation--bone sialoprotein and osteopontin. Differences in the levels of expression of IL-1alpha and TNF-alpha 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. 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-1 alpha (IL-1), IL-1 beta , 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 and lower levels of genes involved in osteoblast maturation-bone sialoprotein and osteopontin. Differences in the levels of expression of IL-1 alpha and TNF- alpha 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. 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. |
Author | Vučenik, Vladimira Kovačić, Nataša Lukić, Ivan Krešimir Grčević, Danka Marušić, Ana Katavić, Vedran Kalajzić, Ivo |
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BackLink | https://www.ncbi.nlm.nih.gov/pubmed/14575809$$D View this record in MEDLINE/PubMed |
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CitedBy_id | crossref_primary_10_3390_antiox11122474 crossref_primary_10_1111_j_1365_2249_2005_02680_x crossref_primary_10_1111_j_1601_6343_2006_00365_x crossref_primary_10_1111_jcpe_13750 crossref_primary_10_3389_fimmu_2021_678873 crossref_primary_10_4049_jimmunol_178_6_3379 crossref_primary_10_1016_j_cellimm_2005_04_010 |
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Keywords | Fas ligand Phenotype Gene knockout Osteoinduction Bone morphogenetic proteins Mice Bone Apoptosis |
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Snippet | 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... |
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SubjectTerms | Animals Apoptosis Blotting, Northern Bone Bone Development - genetics Bone Morphogenetic Protein 2 Bone morphogenetic proteins Bone Morphogenetic Proteins - pharmacology Cartilage - drug effects Cartilage - growth & development Fas ligand Fas Ligand Protein Gene knockout Membrane Glycoproteins - genetics Membrane Glycoproteins - metabolism Membrane Glycoproteins - physiology Mice Mice, Inbred C57BL Osteoinduction Phenotype Point Mutation Polymerase Chain Reaction Recombinant Proteins - pharmacology Transforming Growth Factor beta |
Title | Non-functional Fas ligand increases the formation of cartilage early in the endochondral bone induction by rhBMP-2 |
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