Acroosteolysis in systemic sclerosis: An insight into hypoxia-related pathogenesis

Siao-Pin, Simon; Damian, Laura-Otilia; Muntean, Laura; Rednic, Simona

doi:10.3892/etm.2016.3782

Cited by 20 publications

(16 citation statements)

References 42 publications

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“…In scleroderma, acroosteolysis and condylysis are supposed to be caused by vasculopathy and pressure atrophy secondary to ischemia at the attachment site of muscles. 4–6 Although scleromyxedema generally does not present vasculopathy, our patient had several symptoms related to peripheral circulatory disorders such as coldness and numbness of her hands and feet since she developed skin manifestations. The microvascular impairment revealed by skin biopsy implies dermal/subcutaneous vascular loss and occlusion in her body.…”

Section: Discussionmentioning

confidence: 76%

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Unusual type of scleromyxedema with multiple subcutaneous nodules, IgM-λ paraproteinemia, and scleroderma-like microangiopathy

Awaji

Asano

Takaoka

et al. 2020

Journal of Scleroderma and Related Disorders

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Scleromyxedema is a mysterious cutaneous mucinosis of unknown etiology. Various types of scleromyxedema variant have been reported, which often give us a clue to understand the key aspects of this disease. Here, we describe a woman with highly unusual type of scleromyxedema. In addition to the rare manifestations of multiple subcutaneous nodules and IgM-λ paraproteinemia, our patient showed several characteristic symptoms of scleroderma such as shortened nails and fingertips, sclerodactyly, and bone resorption of fingertips and mandibles as a result of peripheral circulatory insufficiency, although this disease is known to be pathophysiologically different from scleroderma. A skin biopsy revealed cutaneous microvascular stenosis and occlusion due to intravascular mucin deposition and fibrotic changes, suggesting that scleromyxedema potentially develops peripheral circulatory disorders and other vascular involvement. The subcutaneous nodules were responsive to high-dose intravenous immunoglobulin. Scleromyxedema can represent a wide variety of systemic involvement, and therefore, we should pay attention to those symptoms as well as skin lesions.

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Section: Discussionmentioning

confidence: 76%

“…Bone resorption of the fingertips is characteristic of scleroderma, 4 and mandibles can also be affected in some cases. 5 However, no studies of scleromyxedema have reported these symptoms.…”

Section: Discussionmentioning

confidence: 99%

Unusual type of scleromyxedema with multiple subcutaneous nodules, IgM-λ paraproteinemia, and scleroderma-like microangiopathy

Awaji

Asano

Takaoka

et al. 2020

Journal of Scleroderma and Related Disorders

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“…HIF-1α is the master transcriptional regulator of the adaptive response to hypoxia, which is the tightly regulated form of HIF-1, and will quickly be hydroxylated and degraded in normoxic conditions by prolyl hydroxylases [34][35][36][37]. However, in hypoxia conditions, the expression of HIF-1α would dramatically upregulate [38,39].…”

Section: Discussionmentioning

confidence: 99%

Hypoxia induced interstitial transformation of microvascular endothelial cells by mediating HIF-1α/VEGF signaling in systemic scleroderma

Mao

Liu

Wang

et al. 2020

Preprint

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Background: Endothelial mesenchymal transition (EndMT) is a key pathological event for vasculopathy, and is one of the early features and hallmarks of systemic scleroderma (SSc). It has been well-established that hypoxia contributes to EndMT. However, little is known about the effects of EndMT induced by hypoxia on the skin microvascular remodeling of SSc, as well as the underlying mechanism. Methods: Skin biopsy was performed for SSc patients and healthy controls, and skin tissues were collected for isobaric tags for the relative and absolute quantification (iTRAQ)-based proteomics and immunohistochemical test. Human microvascular endothelial cell line-1 (HMEC-1) cultured in hypoxic or normal conditions was treated by tamoxifen or bevacizumab. The expression of hypoxia inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF)-a, CD31, α-smooth muscle actin (α-SMA), VE-cadherin, and fibronectin were detected at both the protein and mRNA level.Results: The iTRAQ-based proteomics indicated the significantly upregulated HIF-1 signal in the skin tissues of SSc patients. The immunohistochemical results demonstrated the significant downregulation of endothelial cell (EC) marker CD31 and the distinct positive staining of interstitial cell (IC) marker α-SMA at sites that lined the vessel lumens in skin tissues of SSc. Meanwhile, the positive staining of HIF-1α, which is a key transcription factor in response to chronic hypoxia, and VEGF-a were found to be diffusely distributed in SSc skin tissues. Consistent with these observations, HMEC-1 cells cultured under hypoxic conditions exhibited a significant decrease in CD31 and VE-cadherin expression, alongside the marked increase in the expression of α-SMA and fibronectin, as well as the distinct upregulation of HIF-1α and VEGF-a, when compared with those under normal conditions. It is noteworthy that the inhibition of HIF-1α by tamoxifen effectively downregulated the hypoxic induction of VEGF-a and α-SMA, while rescuing the hypoxic suppression of CD31. In addition, the VEGF-a inhibitor bevacizumab treatment had the same effect on the hypoxic expression of α-SMA and CD31, as a tamoxifen intervention, but did not reduce HIF-1α. Conclusion: These results suggest that the HIF-1α/VEGF signaling pathway has a critical role in mediating the effect of hypoxia-induced EndMT on the skin microvascular remodeling of SSc.

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“…The course is variable, with osteolysis stabilizing in some patients and progressing towards complete loss of the distal phalanges in others. Osteolysis in SSc is associated with more severe disease, including digital ulceration [25][26][27][28], pulmonary arterial hypertension (PAH) [24], severe digital ischemia [26][27][28], severe calcinosis [24,28,29], and longer disease duration [27,29]. Radiographic progression of flexion contractures has also been reported to be significantly higher in patients Fig.…”

Section: Systemic Sclerosismentioning

confidence: 99%

Lost bones: differential diagnosis of acro-osteolysis seen by the pediatric rheumatologist

et al. 2021

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Introduction Acro-osteolysis is a radiographic finding which refers to bone resorption of the distal phalanges. Acro-osteolysis is associated with various conditions and its presence should prompt the clinician to search for the underlying etiology. The aim of this review is to discuss disorders with which acro-osteolysis is associated and their distinguishing features, with a focus on the pediatric population. Methods A targeted literature review was performed using the term “acro-osteolysis” in combination with other key terms. The primary search results were supplemented using reference citations. Articles published prior to the year 2000 were included if they described additional associations not encountered in the more recent literature. Results Genetic disorders (particularly primary hypertrophic osteoarthropathy and skeletal dysplasias) and rheumatic diseases (particularly psoriatic arthritis and systemic sclerosis) are the most frequently encountered conditions associated with acro-osteolysis in children. Hyperparathyroidism, neuropathy, local trauma and thermal injury, and spinal dysraphism should also be included in the differential diagnosis. Conclusion Although acro-osteolysis is uncommon, its presence should prompt the clinician to consider a differential diagnosis based on clinical and radiographic features.

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Acroosteolysis in systemic sclerosis: An insight into hypoxia-related pathogenesis

Cited by 20 publications

References 42 publications

Unusual type of scleromyxedema with multiple subcutaneous nodules, IgM-λ paraproteinemia, and scleroderma-like microangiopathy

Unusual type of scleromyxedema with multiple subcutaneous nodules, IgM-λ paraproteinemia, and scleroderma-like microangiopathy

Hypoxia induced interstitial transformation of microvascular endothelial cells by mediating HIF-1α/VEGF signaling in systemic scleroderma

Lost bones: differential diagnosis of acro-osteolysis seen by the pediatric rheumatologist

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