&lt;p&gt;Advances in nanomedicine for the treatment of ankylosing spondylitis&lt;/p&gt;

Xi, Yanhai; Jiang, Tingwang; Chaurasiya, Birendra; Zhou, Yumin; Yu, Jiangmin; Wen, Jiankun; Shen, Yan; Ye, Xiaojian; Webster, Thomas J

doi:10.2147/ijn.s216199

Cited by 29 publications

(46 citation statements)

References 171 publications

(142 reference statements)

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“…Ankylosing spondylitis (AS) is a chronic arthritis accompanied by inflammation of bone at the cartilage-bone interface [73,74]. AS develops with time via chronic inflammation mainly in the spine, and extra bone is formed in the spine, followed by the fusion of vertebrae.…”

Section: Ankylosing Spondylitis (As)mentioning

confidence: 99%

“…The functions of HLA-B27 regulate its ability to misfold, to induce an endoplasmic reticulum stress response, and to promote autophagy/unfolded protein responses (UPR). The expression of UPR genes induces inflammatory cytokine production, such as TNF-α and IL-17 from Th17 cells [73,74]. Since AS is an HLA-B27-linked inflammatory disease, AS has been treated with anti-inflammatory or immunosuppressive drugs [73].…”

Section: Ankylosing Spondylitis (As)mentioning

confidence: 99%

“…The expression of UPR genes induces inflammatory cytokine production, such as TNF-α and IL-17 from Th17 cells [73,74]. Since AS is an HLA-B27-linked inflammatory disease, AS has been treated with anti-inflammatory or immunosuppressive drugs [73]. Recent data suggested a role for TNF-α in the pathophysiology of AS and showed that TNF-α mRNA is upregulated in the sacroiliac joints of AS patients.…”

Section: Ankylosing Spondylitis (As)mentioning

confidence: 99%

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The Role of NF-κB in Physiological Bone Development and Inflammatory Bone Diseases: Is NF-κB Inhibition “Killing Two Birds with One Stone”?

Jimi

Takakura

Hiura

et al. 2019

Cells

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Nuclear factor-κB (NF-κB) is a transcription factor that regulates the expression of various genes involved in inflammation and the immune response. The activation of NF-κB occurs via two pathways: inflammatory cytokines, such as TNF-α and IL-1β, activate the “classical pathway”, and cytokines involved in lymph node formation, such as CD40L, activate the “alternative pathway”. NF-κB1 (p50) and NF-κB2 (p52) double-knockout mice exhibited severe osteopetrosis due to the total lack of osteoclasts, suggesting that NF-κB activation is required for osteoclast differentiation. These results indicate that NF-κB may be a therapeutic target for inflammatory bone diseases, such as rheumatoid arthritis and periodontal disease. On the other hand, mice that express the dominant negative form of IκB kinase (IKK)-β specifically in osteoblasts exhibited increased bone mass, but there was no change in osteoclast numbers. Therefore, inhibition of NF-κB is thought to promote bone formation. Taken together, the inhibition of NF-κB leads to “killing two birds with one stone”: it suppresses bone resorption and promotes bone formation. This review describes the role of NF-κB in physiological bone metabolism, pathologic bone destruction, and bone regeneration.

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Section: Ankylosing Spondylitis (As)mentioning

confidence: 99%

Section: Ankylosing Spondylitis (As)mentioning

confidence: 99%

Section: Ankylosing Spondylitis (As)mentioning

confidence: 99%

See 1 more Smart Citation

The Role of NF-κB in Physiological Bone Development and Inflammatory Bone Diseases: Is NF-κB Inhibition “Killing Two Birds with One Stone”?

Jimi

Takakura

Hiura

et al. 2019

Cells

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“…We further assessed the response of the TgA86 model to anti-TNF treatment, a therapy that has been proven e cacious in the early treatment of human SpA patients (25,26). More speci cally, we treated TgA86 mice with Etanercept starting either from 2.5 weeks of age, i.e.…”

Section: Anti-tnf Therapy E Ciently Ameliorates Both Axial and Periphmentioning

confidence: 99%

Ectopic bone formation and systemic bone loss in a transmembrane TNF-driven model of human spondyloarthritis

-Vafeiadou

Geka

Ntari

et al. 2020

Preprint

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Background The transmembrane-TNF transgenic mouse, TgA86, has been shown to develop spontaneously peripheral arthritis with signs of axial involvement. To assess similarity to human spondyloarthritis we performed detailed characterization of the axial, peripheral and comorbid pathologies of this model.Methods TgA86 bone pathologies were assessed at different ages using CT imaging of the spine, tail vertebrae and hind limbs and characterized in detail by histopathological and immunohistochemical analysis. Cardiac function was examined by echocardiography and electrocardiography and bone structural parameters by µCT analysis. The response of TgA86 mice to either early or late anti-TNF treatment was evaluated clinically, histopathologically and by µCT analysis. Results TgA86 mice developed with 100% penetrance spontaneous axial and peripheral pathology which progressed with time and manifested as reduced body weight and body length, kyphosis, tail bendings as well as swollen and distorted hind joints. Whole body CT analysis at advanced ages revealed bone erosions of sacral and caudal vertebrae as well as of sacroiliac joints and hind limps, and also, new ectopic bone formation and eventually vertebral fusion. The pathology of these mice highly resembled that of SpA patients, as it evolved through an early inflammatory phase, evident as enthesitis and synovitis in the affected joints, characterized by mesenchymal cell accumulation and neutrophilic infiltration. Subsequently, regression of inflammation was accompanied by ectopic bone formation, leading to ankylosis. In addition, both systemic bone loss and comorbid heart valve pathology were evident. Importantly, early anti-TNF treatment, similar to clinical treatment protocols, significantly reduced the inflammatory phase of both the axial and peripheral pathology of TgA86 mice. Conclusions The TgA86 mice develop a spontaneous peripheral and axial biphasic pathology accompanied by comorbid heart valvular dysfunction and osteoporosis, overall faithfully reproducing the progression of pathognomonic features of human spondyloarthritis. Therefore, the TgA86 mouse represents a valuable model for deciphering the role of transmembrane TNF in the pathogenic mechanisms of spondyloarthritis and for assessing the efficacy of human therapeutics targeting different phases of the disease.

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“…We further assessed the response of the TgA86 model to anti-TNF treatment, a therapy that has proven efficacious in the early treatment of human SpA patients (22,23). More specifically, we treated TgA86 mice with Etanercept starting either from 2.5 weeks of age, i.e.…”

Section: Anti-tnf Therapy Efficiently Ameliorates Both Axial and Perimentioning

confidence: 99%

Ectopic bone formation and systemic bone loss in a transmembrane TNF-driven model of human spondyloarthritis

Christodoulou-Vafeiadou¹,

Geka²,

Ntari³

et al. 2020

Preprint

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Background The transmembrane-TNF transgenic mouse, TgA86, has been shown to develop spontaneously peripheral arthritis with signs of axial involvement. To assess similarity to human spondyloarthritis we performed detailed characterization of the axial, peripheral and comorbid pathologies of this model. MethodsTgA86 bone pathologies were assessed at different ages using CT imaging of the spine, tail vertebrae and hind limbs and characterized in detail by histopathological and immunohistochemical analysis. Cardiac function was examined by echocardiography and electrocardiography and bone structural parameters by µCT analysis. The response of TgA86 mice to either early or late anti-TNF treatment was evaluated clinically, histopathologically and by µCT analysis. ResultsTgA86 mice developed with 100% penetrance spontaneous axial and peripheral pathology which progressed with time and manifested as reduced body weight and body length, kyphosis, tail bendings as well as swollen and distorted hind joints. Whole body CT analysis at advanced ages revealed bone erosions of sacral and caudal vertebrae as well as of sacroiliac joints and hind limps, and also, new ectopic bone formation and eventually vertebral fusion. The pathology of these mice highly resembled that of SpA patients, as it evolved through an early inflammatory phase, evident as enthesitis and synovitis in the affected joints, characterized by mesenchymal cell accumulation and neutrophilic infiltration. Subsequently, regression of inflammation was accompanied by ectopic bone formation, leading to ankylosis. In addition, both systemic bone loss and comorbid heart valve pathology were evident. Importantly, early anti-TNF treatment, similar to clinical treatment protocols, significantly reduced the inflammatory phase of both the axial and peripheral pathology of TgA86 mice. Conclusions The TgA86 mice develop a spontaneous peripheral and axial biphasic pathology accompanied by comorbid heart valvular dysfunction and osteoporosis, overall faithfully reproducing the progression of pathognomonic features of human spondyloarthritis. Therefore, the TgA86 mouse represents a valuable model for deciphering the pathogenic mechanisms of spondyloarthritis and for assessing the efficacy of human therapeutics targeting different phases of the disease.

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<p>Advances in nanomedicine for the treatment of ankylosing spondylitis</p>

Cited by 29 publications

References 171 publications

The Role of NF-κB in Physiological Bone Development and Inflammatory Bone Diseases: Is NF-κB Inhibition “Killing Two Birds with One Stone”?

The Role of NF-κB in Physiological Bone Development and Inflammatory Bone Diseases: Is NF-κB Inhibition “Killing Two Birds with One Stone”?

Ectopic bone formation and systemic bone loss in a transmembrane TNF-driven model of human spondyloarthritis

Ectopic bone formation and systemic bone loss in a transmembrane TNF-driven model of human spondyloarthritis

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