Contribution of Type H Blood Vessels to Pathologic Osteogenesis and Inflammation in an Experimental Spondyloarthritis Model.

Autor: Kaaij MH; Amsterdam Rheumatology & Immunology Center, and Department of Experimental Immunology, Amsterdam UMC/University of Amsterdam, The Netherlands., van Hamburg JP; Amsterdam Rheumatology & Immunology Center, and Department of Experimental Immunology, Amsterdam UMC/University of Amsterdam, The Netherlands., van Rooijen CCN; Amsterdam Rheumatology & Immunology Center, and Department of Experimental Immunology, Amsterdam UMC/University of Amsterdam, The Netherlands., Grüneboom A; Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich Alexander University Erlangen-Nuremberg and Universitaetsklinikum Erlangen, Erlangen, Germany, and Leibniz-Institut für Analytische Wissenschaften-ISAS-E.V., Dortmund, Germany., Kan YY; Amsterdam Rheumatology & Immunology Center, and Department of Experimental Immunology, Amsterdam UMC/University of Amsterdam, The Netherlands., Pots D; Amsterdam Rheumatology & Immunology Center, and Department of Experimental Immunology, Amsterdam UMC/University of Amsterdam, The Netherlands., Schett G; Department of Internal Medicine 3-Rheumatology and Immunology, and Deutsches Zentrum Immuntherapie, Friedrich Alexander University Erlangen-Nuremberg and Universitaetsklinikum Erlangen, Erlangen, Germany., van Ruijven LJ; Department of Oral Cell Biology, ACTA-University of Amsterdam and VU University, Amsterdam Movement Sciences, Amsterdam, The Netherlands., van Duivenvoorde LM; Amsterdam Rheumatology & Immunology Center, and Department of Experimental Immunology, Amsterdam UMC/University of Amsterdam, The Netherlands., Huitema LFA; Amsterdam Rheumatology & Immunology Center, and Department of Experimental Immunology, Amsterdam UMC/University of Amsterdam, The Netherlands., Baeten DLP; Amsterdam Rheumatology & Immunology Center, and Department of Experimental Immunology, Amsterdam UMC/University of Amsterdam, The Netherlands., Tas SW; Amsterdam Rheumatology & Immunology Center, and Department of Experimental Immunology, Amsterdam UMC/University of Amsterdam, The Netherlands.
Jazyk: angličtina
Zdroj: Arthritis & rheumatology (Hoboken, N.J.) [Arthritis Rheumatol] 2023 Jul; Vol. 75 (7), pp. 1152-1165. Date of Electronic Publication: 2023 Apr 23.
DOI: 10.1002/art.42449
Abstrakt: Objective: Spondyloarthritis (SpA) is characterized by pathologic osteogenesis, inflammation, and extensive angiogenesis in axial and peripheral tissues. Current therapies effectively target inflammation, but these therapies lack efficacy in preventing pathologic osteogenesis. Transgenic mice overexpressing transmembrane tumor necrosis factor (tmTNF-Tg mice) exhibit SpA-like features. We hypothesized that type H blood vessels, which are implicated in osteogenesis, are increased and contribute to pathology in this experimental SpA model.
Methods: We analyzed ankles, femora, and vertebrae of tmTNF-Tg mice and nontransgenic littermates and tmTNF-Tg mice on either a TNF receptor type I (TNFRI)-deficient or TNF receptor type II (TNFRII)-deficient background for osteogenesis, angiogenesis, and inflammation using advanced imaging technologies at various stages of disease.
Results: Compared to nontransgenic littermates, tmTNF-Tg mice exhibited an increase in vertebral type H vessels and osteoprogenitor cells in subchondral bone. These features of increased angiogenesis and osteogenesis were already present before onset of clinical disease symptoms. Type H vessels and osteoprogenitor cells were in close proximity to inflammatory lesions and ectopic lymphoid structures. The tmTNF-Tg mice also showed perivertebral ectopic type H vessels and osteogenesis, an increased number of vertebral transcortical vessels, and enhanced entheseal angiogenesis. In tmTNF-Tg mice crossed on a TNFRI- or TNFRII-deficient background, no clear reduction in type H vessels was shown, suggesting that type H vessel formation is not exclusively mediated via TNFRI or TNFRII.
Conclusion: The contribution of type H vessels to pathologic osteogenesis in experimental SpA advances our knowledge of the pathophysiology of this disease and may also provide a novel opportunity for targeted intervention.
(© 2023 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)
Databáze: MEDLINE
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