title: Tumor Necrosis Factor Alpha Overexpression Induces Mainly Osteoclastogenesis at the Vertebral Site.
abstract: Syndesmophyte occurrence and axial bone loss were investigated in the heterozygous Tg187 tumor necrosis factor (TNF) transgenic mouse model (Tg-huTNF) of arthritis. Female and male Tg-huTNF mice were compared to wild-type mice (WT) at 2, 4, 6, 8, and 10 weeks. Syndesmophytes, intervertebral disc space, osteoclasts, osteoid surface, and vertebra microarchitecture were assessed by histomorphometry and microcomputed tomography. No spontaneous syndesmophyte formation was detected in Tg-huTNF compared to WT mice. However, increased porosity was observed mainly in peridiscal lumbar vertebra. Accordingly, bone microarchitecture parameters were altered in Tg-huTNF mice, with decrease in bone volume fraction, and trabecular number and thickness after 6 weeks compared to WT (p < 0.05). Osteoclast count and surface were increased (p < 0.01). Moreover, the non-mineralized (osteoid) surface was also increased in Tg-huTNF after 6 weeks (p < 0.01). Despite increased osteoclast and osteoid surfaces, an imbalance between both was observed in favour of osteoid surface at the early phase and then to osteoclast surface. These results demonstrated an axial bone loss in the Tg-huTNF model, additional to the common limb arthritis, related to overexpression of TNF. However, the absence of syndesmophyte and the increase of osteoid surface suggested that chronic inflammation might block bone mineralisation. Finally, the relative increased osteoid surface was not enough to compensate the high osteoclast activity.
authors.affiliation: SAINBIOSE, INSERM, U1059, LBTO, 42023, Saint-Etienne, France.|University of Lyon, Saint-Etienne, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Courbon
authors.affiliation: INSERM, UMR1033, University Claude Bernard Lyon 1, UFR de Médecine Lyon Est, Rue Guillaume Paradin, 69372, Lyon Cedex 08, France.|University of Lyon I, Lyon, France.
authors.forename: Sacha
authors.initials: S
authors.lastname: Flammier
authors.affiliation: SAINBIOSE, INSERM, U1059, LBTO, 42023, Saint-Etienne, France.|University of Lyon, Saint-Etienne, France.
authors.forename: Norbert
authors.initials: N
authors.lastname: Laroche
authors.affiliation: SAINBIOSE, INSERM, U1059, LBTO, 42023, Saint-Etienne, France.|University of Lyon, Saint-Etienne, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Vico
authors.affiliation: SAINBIOSE, INSERM, U1059, LBTO, 42023, Saint-Etienne, France. hubert.marotte@chu-st-etienne.fr.|University of Lyon, Saint-Etienne, France. hubert.marotte@chu-st-etienne.fr.|Department of Rheumatology, University Hospital of Saint-Etienne, 42055, Saint-Etienne, France. hubert.marotte@chu-st-etienne.fr.
authors.forename: Hubert
authors.initials: H
authors.lastname: Marotte
authors.affiliation: INSERM, UMR1033, University Claude Bernard Lyon 1, UFR de Médecine Lyon Est, Rue Guillaume Paradin, 69372, Lyon Cedex 08, France. fabienne.coury@free.fr.|University of Lyon I, Lyon, France. fabienne.coury@free.fr.|Institut de Génomique Fonctionnelle de Lyon, UMR 5242 CNRS/Ecole Normale Supérieure de Lyon, Lyon, France. fabienne.coury@free.fr.|Department of Rheumatology, Lyon Sud Hospital, Lyon, France. fabienne.coury@free.fr.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Coury
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000378:metabolism; D001842:Bone and Bones / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism*; D010012:Osteogenesis / Q000502:physiology*; D013131:Spine / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D014409:Tumor Necrosis Factor-alpha
keywords: Axial spondylitis; Bone microarchitecture; Bone remodelling; TNF