TY - JOUR
T1 - Contribution of Type H Blood Vessels to Pathologic Osteogenesis and Inflammation in an Experimental Spondyloarthritis Model
AU - Kaaij, Merlijn H.
AU - van Hamburg, Jan Piet
AU - van Rooijen, Charlotte C.N.
AU - Grüneboom, Anika
AU - Kan, Yik Y.
AU - Pots, Desiree
AU - Schett, Georg
AU - van Ruijven, Leo J.
AU - van Duivenvoorde, Leonie M.
AU - Huitema, Leonie F.A.
AU - Baeten, Dominique L.P.
AU - Tas, Sander W.
N1 - Funding Information: Supported by the Dutch Arthritis Foundation grant 15‐2‐401. Dr. Schett's work was supported by the Deutsche Forschungsgemeinschaft through projects CRC1181 and FOR 2886, the Federal Ministry for Science and Education through the project MASCARA, the European Research Council through the project 4D Nanoscope, and the Innovative Medicine Initiative through the project Hippocrates. Publisher Copyright: © 2023 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.
PY - 2023/7
Y1 - 2023/7
N2 - 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.
AB - 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.
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U2 - https://doi.org/10.1002/art.42449
DO - https://doi.org/10.1002/art.42449
M3 - Article
C2 - 36657110
SN - 2326-5191
VL - 75
SP - 1152
EP - 1165
JO - Arthritis and Rheumatology
JF - Arthritis and Rheumatology
IS - 7
ER -