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Tumor Necrosis Factor Alpha Overexpression Induces Mainly Osteoclastogenesis at the Vertebral Site

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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.

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Acknowledgements

We thank Dr Georg Kollias (Fleming Research Center, Greece) for kindly providing Tg-huTNF mice. This work was supported by a grant Passerelle from Pfizer to FC.

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    Authors and Affiliations

    1. SAINBIOSE, INSERM, U1059, LBTO, 42023, Saint-Etienne, France

      Guillaume Courbon, Norbert Laroche, Laurence Vico & Hubert Marotte

    2. University of Lyon, Saint-Etienne, France

      Guillaume Courbon, Norbert Laroche, Laurence Vico & Hubert Marotte

    3. INSERM, UMR1033, University Claude Bernard Lyon 1, UFR de Médecine Lyon Est, Rue Guillaume Paradin, 69372, Lyon Cedex 08, France

      Sacha Flammier & Fabienne Coury

    4. University of Lyon I, Lyon, France

      Sacha Flammier & Fabienne Coury

    5. Department of Rheumatology, University Hospital of Saint-Etienne, 42055, Saint-Etienne, France

      Hubert Marotte

    6. Institut de Génomique Fonctionnelle de Lyon, UMR 5242 CNRS/Ecole Normale Supérieure de Lyon, Lyon, France

      Fabienne Coury

    7. Department of Rheumatology, Lyon Sud Hospital, Lyon, France

      Fabienne Coury

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    1. Guillaume Courbon
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    Correspondence to Hubert Marotte or Fabienne Coury.

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    Guillaume Courbon, Sacha Flammier, Norbert Laroche, Laurence Vico, Hubert Marotte, and Fabienne Coury declare that they have no conflict of interest.

    Human and Animal Rights and Informed Consent

    All experimental procedures were approved by our local animal experimentation ethics committee (CECCAPP; permit number for animal experimentation 69387429 Lyon, France).

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    Hubert Marotte and Fabienne Coury have contributed equally to this work.

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    Courbon, G., Flammier, S., Laroche, N. et al. Tumor Necrosis Factor Alpha Overexpression Induces Mainly Osteoclastogenesis at the Vertebral Site. Calcif Tissue Int 100, 575–584 (2017). https://doi.org/10.1007/s00223-017-0237-8

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    • DOI: https://doi.org/10.1007/s00223-017-0237-8

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