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
Main Authors: Katavic, V, Grcevic, D, Lukic, I K, Vucenik, V, Kovacic, N, Kalajzic, I, Marusic, A
Format: Journal Article
Language:English
Published: Netherlands Elsevier Inc 21-11-2003
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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.
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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Issue 1
Keywords Fas ligand
Phenotype
Gene knockout
Osteoinduction
Bone morphogenetic proteins
Mice
Bone
Apoptosis
Language English
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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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StartPage 13
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
URI https://dx.doi.org/10.1016/j.lfs.2003.06.031
https://www.ncbi.nlm.nih.gov/pubmed/14575809
https://search.proquest.com/docview/18955996
https://search.proquest.com/docview/71307300
Volume 74
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