Early sclerostin expression explains bone formation inhibition before arthritis onset in the rat adjuvant-induced arthritis model

Courbon, Guillaume; Lamarque, R; Gerbaix, Maude; Caire, Robin; Linossier, Marie‐Thérèse; Laroche, Norbert; Thomas, Mireille; Thomas, Thierry; Vico, Laurence; Marotte, Hubert

doi:10.1038/s41598-018-21886-w

Cited by 20 publications

(17 citation statements)

References 47 publications

(63 reference statements)

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“…Rat ankle bone loss following oral P. gingivalis exposure was observed after 8 months of initial P. gingivalis exposure. P. gingivalis induced is comparable to the bone loss observed during other experimental RA models such as the rat adjuvant-induced arthritis model 17. As in patients with RA, bone loss was mostly related to osteoclast activation.…”

Section: Discussionsupporting

confidence: 71%

Porphyromonas gingivalis experimentally induces periodontis and an anti-CCP2-associated arthritis in the rat

et al. 2019

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ObjectivesAssociation between periodontal disease (PD) and rheumatoid arthritis (RA) has been extensively described, but direct evidence of causal involvement of PD in RA is missing. We investigated the priming role of oral Porphyromonas gingivalis (P. gingivalis) in PD and subsequent RA and we assessed biomarkers of bone resorption and arthritis development in rats.MethodsLewis rats were orally exposed to either P. gingivalis, Prevotella intermedia or control gel for 1 month and then followed for 8 months. The onset and development of PD was assessed by serology, gingivitis severity and micro-CT (µCT). We investigated arthritis development using circulating proinflammatory markers, anticyclic citrullinated peptide (CCP), anticitrullinated protein antibody (ACPA), ankle histology and µCT.ResultsPD was only observed in the P. gingivalis treated rats, as early as 1 month postexposure. Joint and systemic inflammation were detected only in the P. gingivalis group after 4 and 8 months. At 8 months, inflammatory cell infiltrate was observed in ankle joints and paralleled cortical erosions and overall cortical bone reduction. Furthermore, anti-CCP2 correlated with local and systemic bone loss.ConclusionsIn our long-term study, PD induced by oral exposure to P. gingivalis triggered seropositive arthritis, with systemic inflammation and bone erosions. This is the first in vivo demonstration of arthritis induced by oral priming with P. gingivalis.

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Section: Discussionsupporting

confidence: 71%

Porphyromonas gingivalis experimentally induces periodontis and an anti-CCP2-associated arthritis in the rat

et al. 2019

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“…Pathological bone erosion begins early in RA-in the first months of the clinical disease or even before the onset of clinical symptoms [16,[22][23][24]. This suggests the existence of an additional, at least partially independent from synovial inflammation, mechanism for osteoclast stimulation and bone destruction in RA.…”

Section: Discussionmentioning

confidence: 99%

Antibodies to Citrullinated Proteins (ACPA) Associate with Markers of Osteoclast Activation and Bone Destruction in the Bone Marrow of Patients with Rheumatoid Arthritis

Kurowska

Słowińska

Krogulec

et al. 2021

JCM

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Normalizing bone metabolism is a challenge in rheumatoid arthritis (RA). Studies in mice suggest that anti-citrullinated protein antibodies (ACPAs) can trigger osteoclast activation and bone resorption in the bone marrow. However, data on the presence and role of ACPAs in human bone marrow are scarce. We investigated whether ACPAs can contribute to osteoclast activation and bone erosion in RA bone marrow. Anti-cyclic citrullinated peptide antibodies (anti-CCP Abs), osteoclast activation indicators–the tartrate-resistant acid phosphatase 5b (TRAP5b) and cathepsin K, and bone degradation marker–C-terminal telopeptide of type I collagen (CTX-I) were measured in the bone marrow and peripheral blood of RA patients using ELISAs. We found that ACPAs present in RA bone marrow was associated with increased amounts of TRAP5b, cathepsin K and CTX-I in this location. Levels of IL-8, the key mediator of anti-citrullinated protein antibody (ACPA)-induced bone resorption, were also elevated in bone marrow containing anti-CCP Abs and positively correlated with TRAP5b and cathepsin K concentrations. Higher levels of TRAP5b, cathepsin K, CTX-I and IL-8 in bone marrow compared to peripheral blood indicate local generation of these molecules. Our results complement data from animal studies and highlight the relevance of ACPAs and bone marrow in bone resorption in RA.

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“…TIE-2; VCAM-1 vascular cell adhesion protein 1; endoglin; VEGF-A vascular endothelial growth factor A; CRP C-reactive protein, cutoff level 5 mg/L; ESR erythrocyte sedimentation rate; IL-6 interleukin-6; CD40 ligand; IL-33 interleukin-33 and TNF-α tumour necrosis factor alpha. www.nature.com/scientificreports/ arthritis-associated bone degradation with erosions that is linked to increased levels of DKK-1 and SOST, which is also an integral part of SpA 34 . IL-31 is part of the IL-6 family of cytokines and a preliminary study suggests that high baseline IL-31 levels are not only associated with reduced new bone formation based on the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) in early SpA, but also with low bone mineral density 28 .…”

Section: Discussionmentioning

confidence: 99%

Anti-IL-17A treatment reduces serum inflammatory, angiogenic and tissue remodeling biomarkers accompanied by less synovial high endothelial venules in peripheral spondyloarthritis

Kaaij

Helder

Mens

et al. 2020

Sci Rep

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Spondyloarthritis (SpA) is characterized by inflammation and new bone formation. The exact pathophysiology underlying these processes remains elusive. We propose that the extensive neoangiogenesis in SpA could play a role both in sustaining/enhancing inflammation and in new bone formation. While ample data is available on effects of anti-TNF on angiogenesis, effects of IL-17A blockade on serum markers are largely unknown. We aimed to assess the impact of secukinumab (anti-IL-17A) on synovial neoangiogenesis in peripheral SpA, and how this related to changes in inflammatory and tissue remodeling biomarkers. Serum samples from 20 active peripheral SpA patients included in a 12 week open-label trial with secukinumab were analyzed for several markers of angiogenesis and tissue remodeling. Synovial biopsies taken before and after treatment were stained for vascular markers. Serum levels of MMP-3, osteopontin, IL-6 (all P < 0.001), IL-31, S100A8, S100A9, Vascular Endothelial Growth Factor A (VEGF-A), IL-33, TNF-α (all P < 0.05) decreased significantly upon anti-IL17A treatment. Secukinumab treatment resulted in a decrease in the number of synovial high endothelial venules and lymphoid aggregate score. These results indicate that anti-IL-17A not only diminishes inflammation, but also impacts angiogenesis and tissue remodeling/new bone formation. This may have important implications for disease progression and/or structural damage.

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Early sclerostin expression explains bone formation inhibition before arthritis onset in the rat adjuvant-induced arthritis model

Cited by 20 publications

References 47 publications

Porphyromonas gingivalis experimentally induces periodontis and an anti-CCP2-associated arthritis in the rat

Porphyromonas gingivalis experimentally induces periodontis and an anti-CCP2-associated arthritis in the rat

Antibodies to Citrullinated Proteins (ACPA) Associate with Markers of Osteoclast Activation and Bone Destruction in the Bone Marrow of Patients with Rheumatoid Arthritis

Anti-IL-17A treatment reduces serum inflammatory, angiogenic and tissue remodeling biomarkers accompanied by less synovial high endothelial venules in peripheral spondyloarthritis

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