title: Alteration of newly induced endochondral bone formation in adult mice without tumour necrosis factor receptor 1.
abstract: Tumour necrosis factor (TNF)-alpha, a major proinflammatory cytokine, exerts its role on bone cells through two receptors (TNFR1 and TNFR2). TNFR1, but not TNFR2, is expressed by osteoblasts and its function in bone formation in vivo is not fully understood. We compared in vivo new bone formation in TNFR1-deficient (TNFR1(-/-)) mice and wild-type mice, using two models of bone formation: intramembranous ossification following tibial marrow ablation and endochondral ossification induced by bone morphogenetic protein (BMP)-2. Intramembranous osteogenesis in TNFR1(-/-) mice did not differ from the wild-type mice either in histomorphometric parameters or mRNA expression of bone-related markers and inflammatory cytokines. During endochondral osteogenesis, TNFR1(-/-) mice formed more cartilage (at post-implantation day 9), followed by more bone and bone marrow (at day 12). mRNAs for BMP-2, -4 and -7 were increased during the endochondral differentiation sequence in TNFR1(-/-) mice. The expression of receptor activator of NF-kappa B ligand (RANKL) and receptor activator of NF-kappa B (RANK), as assessed by quantitative reverse transcription polymerase chain reaction (RT-PCR), was also increased significantly during endochondral ossification in TNFR1(-/-) mice. In conclusion, signalling through the TNFR1 seems to be a negative regulator of new tissue formation during endochondral but not intramembranous osteogenesis in an adult organism. BMPs and RANKL and its receptor RANK may be involved in the change of local environment in the absence of TNFR1 signalling.
authors.affiliation: Department of Anatomy, Zagreb University School of Medicine, Zagreb, Croatia. iklukic@mef.hr
authors.forename: I K
authors.initials: IK
authors.lastname: Lukić
authors.forename: D
authors.initials: D
authors.lastname: Grcević
authors.forename: N
authors.initials: N
authors.lastname: Kovacić
authors.forename: V
authors.initials: V
authors.lastname: Katavić
authors.forename: S
authors.initials: S
authors.lastname: Ivcević
authors.forename: I
authors.initials: I
authors.lastname: Kalajzić
authors.forename: A
authors.initials: A
authors.lastname: Marusić
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000378:metabolism / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics; D002356:Cartilage / Q000502:physiology*; D020219:Chondrogenesis / Q000502:physiology; D005260:Female; D006023:Glycoproteins / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010012:Osteogenesis; D053244:Osteoprotegerin; D016133:Polymerase Chain Reaction / Q000379:methods; D053245:RANK Ligand; D012333:RNA, Messenger / Q000032:analysis; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction; D013977:Tibia; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology
chemical_list: D015415:Biomarkers; C525719:Bmp2 protein, mouse; C525810:Bmp4 protein, mouse; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D011994:Recombinant Proteins; C505687:Tnfrsf11a protein, mouse; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D016212:Transforming Growth Factor beta