scholarly journals Fibroblast-Like Synoviocytes Induce Calcium Mineral Formation and Deposition

Arthritis ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Yubo Sun ◽  
David R. Mauerhan ◽  
Atiya M. Franklin ◽  
Natalia Zinchenko ◽  
Harry James Norton ◽  
...  
Keyword(s):  
Calcium Deposition ◽  
Mineral Formation ◽  
Mineral Deposition ◽  
Birefringent Crystals ◽  
Related Transcription Factor ◽  
Calcium Deposits ◽  
Pathological Calcification ◽  
Calcification Process ◽  
Calcium Minerals ◽  
Fibroblast Like Synoviocytes

Calcium crystals are present in the synovial fluid of 65%–100% patients with osteoarthritis (OA) and 20%–39% patients with rheumatoid arthritis (RA). This study sought to investigate the role of fibroblast-like synoviocytes (FLSs) in calcium mineral formation. We found that numerous genes classified in the biomineral formation process, including bone gamma-carboxyglutamate (gla) protein/osteocalcin, runt-related transcription factor 2, ankylosis progressive homolog, and parathyroid hormone-like hormone, were differentially expressed in the OA and RA FLSs. Calcium deposits were detected in FLSs cultured in regular medium in the presence of ATP and FLSs cultured in chondrogenesis medium in the absence of ATP. More calcium minerals were deposited in the cultures of OA FLSs than in the cultures of RA FLSs. Examination of the micromass stained with nonaqueous alcoholic eosin indicated the presence of birefringent crystals. Phosphocitrate inhibited the OA FLSs-mediated calcium mineral deposition. These findings together suggest that OA FLSs are not passive bystanders but are active players in the pathological calcification process occurring in OA and that potential calcification stimuli for OA FLSs-mediated calcium deposition include ATP and certain unidentified differentiation-inducing factor(s). The OA FLSs-mediated pathological calcification process is a valid target for the development of disease-modifying drug for OA therapy.

scholarly journals Biological Effects of Phosphate on Fibroblast-Like Synoviocytes

2012 ◽  
Vol 2012 ◽  
pp. 1-6
Author(s):  
Yubo Sun ◽  
David R. Mauerhan ◽  
Deepthi Chaturvedi ◽  
Edward N. Hanley ◽  
Helen E. Gruber
Keyword(s):  
Cell Death ◽  
Biological Effects ◽  
Interleukin 1 ◽  
Phosphate Transport ◽  
Dependent Manner ◽  
Expression Of Genes ◽  
Calcium Deposits ◽  
Calcification Inhibitors ◽  
Pathological Calcification ◽  
Fibroblast Like Synoviocytes

This study sought to examine the expression of genes implicated in phosphate transport and pathological calcification in osteoarthritis (OA) and rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) and investigate the biological effects of phosphate. Results revealed that several genes, which were implicated in phosphate transport and pathological calcification, were differentially expressed in OA FLS and RA FLS. Phosphate stimulated the expression of matrix metalloproteinse-1, matrix metalloproteinse-3, cyclooxygenase-2, and interleukin-1β in a dose-dependent manner. Phosphate also induced OA FLS cell death but not RA FLS cell death at higher concentration. Calcification inhibitors, phosphocitrate (PC), and ethane-1-hydroxy-1,1-diphosphonate (EHDP), effectively inhibited these detrimental biological effects of phosphate. These findings suggest that abnormal expression of genes implicated in phosphate transport and pathological calcification may contribute to the progression of OA through the induction of extracellular matrix-degrading enzymes, proinflammatory cytokines, cell death, and calcium deposits. Calcification inhibitors such as PC and EHDP are potent inhibitors of these detrimental biological effects of phosphate.

scholarly journals Calcinosis cutis associated with systemic sclerosis: a rare case report

2020 ◽  
Vol 7 (8) ◽  
pp. 2803
Author(s):  
Surya Rao Rao Venkata Mahipathy ◽  
Alagar Raja Durairaj ◽  
Narayanamurthy Sundaramurthy ◽  
Anand Prasath Jayachandiran
Keyword(s):  
Systemic Sclerosis ◽  
The Body ◽  
Calcium Deposition ◽  
Pressure Sores ◽  
Connective Tissue Disorders ◽  
Calcinosis Cutis ◽  
Rare Case Report ◽  
The Face ◽  
Subcutaneous Tissues ◽  
Calcium Deposits

Calcinosis cutis is abnormal calcium deposition in the skin and subcutaneous tissues of the body. It is generally associated with autoimmune connective tissue disorders and in our case, it is systemic sclerosis. It most commonly occurs in the fingers presenting with pain and functional impairment. Here, we present a case of calcinosis cutis with systemic sclerosis in a teenage girl presented with bilateral gluteal pressure sores and multiple sites of calcium deposition like sacrum, upper limbs, knees and the face. We treated here with reconstructive surgery with Limberg flaps for the pressure ulcers with excision and primary closure of the other sites with calcium deposits. 

The fate of calcium in the diet of Rhodnius prolixus: storage in concretion bodies in the Malpighian tubules

1991 ◽  
Vol 157 (1) ◽  
pp. 483-502 ◽  
Author(s):  
S. H. Maddrell ◽  
G. Whittembury ◽  
R. L. Mooney ◽  
J. B. Harrison ◽  
J. A. Overton ◽  
...  
Keyword(s):  
Calcium Concentration ◽  
Rhodnius Prolixus ◽  
The Body ◽  
Malpighian Tubules ◽  
Calcium Deposition ◽  
X Ray Diffraction ◽  
Calcium Deposits ◽  
Membrane Bound ◽  
High Concentrations

We have investigated the fate of the large amounts of calcium ingested by Rhodnius prolixus in its meals of blood. 45Ca2+ injected into the haemolymph or fed to fifth-stage Rhodnius reared on rabbits is accumulated at high concentrations in the cells of the upper Malpighian tubules; very little is excreted from the body This 45Ca2+ accumulation goes on continuously for at least 12 days and the rate of uptake is increased several-fold within 3–4 days of a meal. The extent of calcium accumulation in tubule cells is correlated with the presence of intracellular membrane-bound concretion bodies, which are therefore likely sites of calcium deposition. X-ray diffraction showed that the calcium deposits are non-crystalline. Tubules from rabbit-fed fifth-stage Rhodnius contain 410 mmol l-1 calcium; in those from chicken-fed insects the calcium concentration is over 1 mol l-1; and in those fed in vitro on heparinised low-K+ sheep blood the calcium concentration is only 21 mmol l-1. The concentration of calcium in the haemolymph in all these insects was 8 mmol l-1 and its activity determined by an ion-selective electrode was 2.5 mmol l-1. 45Ca2+ deposited in the tubules is readily exchangeable, but the efflux preferentially passes to the haemolymph side of the tubule epithelium. The ability to sequester calcium in the Malpighian tubules may prevent calcium from interfering with reabsorptive processes in the rectum.

scholarly journals Natural and non-natural antioxidative compounds: potential candidates for treatment of vascular calcification

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Chia-Ter Chao ◽  
Hsiang-Yuan Yeh ◽  
You-Tien Tsai ◽  
Pei-Huan Chuang ◽  
Tzu-Hang Yuan ◽  
...  
Keyword(s):  
Vascular Calcification ◽  
Treatment Options ◽  
Antioxidant Properties ◽  
Vascular Wall ◽  
Calcium Deposition ◽  
Clinical Settings ◽  
Phenotypic Switch ◽  
Mineral Deposition ◽  
Promising Treatment ◽  
Anti Inflammation

Abstract Vascular calcification (VC) is highly prevalent in patients with advanced age, or those with chronic kidney disease and diabetes, accounting for substantial global cardiovascular burden. The pathophysiology of VC involves active mineral deposition by transdifferentiated vascular smooth muscle cells exhibiting osteoblast-like behavior, building upon cores with or without apoptotic bodies. Oxidative stress drives the progression of the cellular phenotypic switch and calcium deposition in the vascular wall. In this review, we discuss potential compounds that shield these cells from the detrimental influences of reactive oxygen species as promising treatment options for VC. A comprehensive summary of the current literature regarding antioxidants for VC is important, as no effective therapy is currently available for this disease. We systematically searched through the existing literature to identify original articles investigating traditional antioxidants and novel compounds with antioxidant properties with regard to their effectiveness against VC in experimental or clinical settings. We uncovered 36 compounds with antioxidant properties against VC pathology, involving mechanisms such as suppression of NADPH oxidase, BMP-2, and Wnt/β-catenin; anti-inflammation; and activation of Nrf2 pathways. Only two compounds have been tested clinically. These findings suggest that a considerable opportunity exists to harness these antioxidants for therapeutic use for VC. In order to achieve this goal, more translational studies are needed.

Unspliced XBP1 Counteracts β-catenin to Inhibit Vascular Calcification

2021 ◽  
Author(s):  
Liu Yang ◽  
Rongbo Dai ◽  
Hao Wu ◽  
Zeyu Cai ◽  
Nan Xie ◽  
...  
Keyword(s):  
Vascular Calcification ◽  
Glycogen Synthase ◽  
Vascular Diseases ◽  
Proteasomal Degradation ◽  
Calcium Deposition ◽  
Alizarin Red ◽  
Protein Levels ◽  
Cardiovascular Morbidity And Mortality ◽  
Related Transcription Factor ◽  
Gsk 3Β

Background: Vascular calcification is a prevalent complication in chronic kidney disease and contributes to increased cardiovascular morbidity and mortality. XBP1 (X-box binding protein 1), existing as the unspliced (XBP1u) and spliced (XBP1s) forms, is a key component of the endoplasmic reticulum stress involved in vascular diseases. However, whether XBP1u participates in the development of vascular calcification remains unclear. Methods: We aim to investigate the role of XBP1u in vascular calcification.XBP1u protein levels were reduced in high phosphate (Pi)-induced calcified vascular smooth muscle cells (VSMCs), calcified aortas from mice with adenine diet-induced chronic renal failure (CRF) and calcified radial arteries from CRF patients. Results: Inhibition of XBP1u rather than XBP1s upregulated in the expression of the osteogenic markers runt-related transcription factor 2 (Runx2) and msh homeobox2 (Msx2), and exacerbated high Pi-induced VSMC calcification, as verified by calcium deposition and Alizarin red S staining. In contrast, XBP1u overexpression in high Pi-induced VSMCs significantly inhibited osteogenic differentiation and calcification. Consistently, SMC-specific XBP1 deficiency in mice markedly aggravated the adenine diet- and 5/6 nephrectomy-induced vascular calcification compared with that in the control littermates. Further interactome analysis revealed that XBP1u bound directly to β-catenin, a key regulator of vascular calcification, via aa 205-230 in its C-terminal degradation domain. XBP1u interacted with β-catenin to promote its ubiquitin-proteasomal degradation and thus inhibited β-catenin/T-cell factor (TCF)-mediated Runx2 and Msx2 transcription. Knockdown of β-catenin abolished the effect of XBP1u deficiency on VSMC calcification, suggesting a β-catenin-mediated mechanism. Moreover, the degradation of β-catenin promoted by XBP1u was independent of glycogen synthase kinase 3β (GSK-3β)-involved destruction complex. Conclusions: Our study identified XBP1u as a novel endogenous inhibitor of vascular calcification by counteracting β-catenin and promoting its ubiquitin-proteasomal degradation, which represents a new regulatory pathway of β-catenin and a promising target for vascular calcification treatment.

scholarly journals Dimethyloxalylglycine Promotes Bone Marrow Mesenchymal Stem Cell Osteogenesis via Rho/ROCK Signaling

2016 ◽  
Vol 39 (4) ◽  
pp. 1391-1403 ◽  
Author(s):  
Lei Zhang ◽  
Guoliang Jiang ◽  
Xueling Zhao ◽  
Yuekun Gong
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Coiled Coil ◽  
Calcium Deposition ◽  
Mrna Levels ◽  
Osteogenic Induction ◽  
Calcium Deposits ◽  
Rock Activity

Background/Aims: We investigated the role of dimethyloxalylglycine (DMOG) in bone marrow mesenchymal stem cell (BMSC) osteogenesis mediated by RhoA/ROCK. Methods: BMSCs were cultured with and without DMOG and/or Y-27632 (ROCK1 inhibitor). Cell proliferation, alkaline phosphatase (ALP) levels, and calcium deposits were determined. The expression of Runx2, OSX, p-cofilin, RhoA, and GTP-bound RhoA was determined by real-time RT-PCR and Western blot. Rho-associated coiled-coil-containing protein kinase (ROCK) activity was determined by measuring the phosphorylation of myosin-binding subunit of myosin phosphatase using an ELISA kit. Actin morphology was observed by immunofluorescence. Results: After 24 h, DMOG (0.5 mM) increased the expression of GTP-bound RhoA (+141%, P < 0.001) and enhanced ROCK activity (315%, P < 0.001). DMOG (0.5 mM) enhanced ALP levels after 3, 7, and 21 days of osteogenic induction (all P < 0.001) and strengthened calcium deposition (P < 0.001). In addition, compared with controls, DMOG (0.5 mM) increased the mRNA levels of osteogenesis genes RUNX2 and OSX (all P < 0.001). Furthermore, compared with controls, DMOG increased the expression of p-cofilin (+57%, P < 0.001), which resulted in rearrangement of actin filaments. All these effects were abolished, at least in part, by Y-27632. Conclusion: DMOG promotes BMSC osteogenic differentiation via activation of RhoA/ROCK, suggesting clues for future therapies using BMSCs.

scholarly journals Pro-calcifying analysis of uraemic serum from patients treated with medium cut-off membrane in a prospective, cross-over study

2020 ◽  
Author(s):  
Paola Ciceri ◽  
Giorgia Tettamanti ◽  
Andrea Galassi ◽  
Lorenza Magagnoli ◽  
Nicolas Fabresse ◽  
...  
Keyword(s):  
Osteoblastic Differentiation ◽  
Water Soluble ◽  
Matrix Gla Protein ◽  
Bone Morphogenetic Protein 2 ◽  
Calcium Deposition ◽  
Open Label ◽  
Small Water ◽  
Middle Molecules ◽  
Related Transcription Factor ◽  
The Difference

Abstract Background The retention of a large number of solutes that are normally excreted or metabolized by the kidney is responsible for the symptoms typical in uraemic patients. These molecules are defined as uraemic toxins and can be classified into three groups: small water-soluble molecules, middle molecules and protein-bound toxins. Recently, efforts were put towards developing dialysis membranes that allow the removal of large middle molecules without clinically relevant albumin loss. These membranes are the medium cut-off (MCO) membranes that allow the removal of middle molecules up to ∼50 000 Da. Methods We performed a prospective, open-label, controlled, cross-over pilot study comparing expanded haemodialysis (HDx) (novel MCO membrane Theranova 400) and conventional haemodialysis (HD) in 20 prevalent HD patients. Ten patients used conventional HD high-flux dialyser and 10 patients used HDx for 3 months; later the patients switched and received the other treatment for a further 3 months. We then analysed the pro-calcifying effect of uraemic serum in a model of high phosphate(Pi)–induced calcification in vascular smooth muscle cells (VSMCs). Results In this study, every patient was the control of himself and, interestingly, we found a tendency of less pro-calcifying potential from HDx-treated patients’ serum compared with HD. Studying pathogenetic processes involved in high Pi–induced calcium deposition, we found that uraemic serum of HDx-treated patients induced less VSMC necrosis compared with uraemic serum of HD patients. Nevertheless, no differences were found between the different dialytic treatments in the serum potential to induce apoptosis and to modulate the expression of a panel of genes involved in VSMC simil-osteoblastic differentiation such as bone morphogenetic protein 2, runt-related transcription factor 2, osteocalcin, matrix Gla protein, osteopontin, elastin and collagen I α1. In an effort to characterize the difference in uraemic toxin profile during the two different dialytic treatments, we measured a panel of 10 uraemic toxins and 3 precursors, finding a significant increased removal during HDx of 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid, tryptophane and some of its metabolites, such as 3-indoxyl sulphate, indole 3-acetic acid and kynurenine. Conclusions These preliminary data are promising, although larger patients’ groups are needed to better understand the effects of HDx on vascular calcification.

Spontaneous Calcium Deposition in the Scaffolds from Human Dermal Solutions

2012 ◽  
Vol 506 ◽  
pp. 138-141
Author(s):  
K. Theerakittayakorn ◽  
T. Bunprasert
Keyword(s):  
Tissue Engineering ◽  
Type I Collagen ◽  
Collagen Matrix ◽  
Raw Material ◽  
Calcium Deposition ◽  
Type I ◽  
Human Dermis ◽  
Calcium Deposits ◽  
Scaffold Materials ◽  
Bovine Type

Human dermis was used as a new source of raw material for tissue engineering scaffold fabrication. Three human dermal solutions were prepared from different fractions after centrifugation and denoted as DS-1, DS-2 and DS-3. Approximately, the ratios of sulfated GAGs to collagen were 0.03, 0.02 and 0.04 for DS-1, DS-2 and DS-3, respectively. Scaffolds from the human dermal solutions and the commercial bovine type I collagen (Sigma®, St. Louis, MO, USA) were fabricated. The scaffolds were submerged in the normal culture medium and the calcium depositions were determined at day 1, 7 and 21. The highest calcium deposit was found in the scaffolds from type I collagen, the second were the scaffolds from DS-2, the third were the scaffolds from DS-1 and the lowest were the scaffolds from DS-3 for all time points. Histological sections stained with von Kossa stain explicitly exhibit the calcium depositions in the scaffolds. The calcium deposited in a manner according to the sulfated GAGs/collagen ratios of the scaffold materials. Calcium deposits are naturally incoperated into the collagen matrix of the human dermal solution-derived scaffolds. In bone tissue engineering, interpretation of experimental results should be careful of the spontaneous calcium deposition in scaffolds from collagen.

scholarly journals Evaluation of BMP-2 Enhances the Osteoblast Differentiation of Human Amnion Mesenchymal Stem Cells Seeded on Nano-Hydroxyapatite/Collagen/Poly(l-Lactide)

2018 ◽  
Vol 19 (8) ◽  
pp. 2171 ◽  
Author(s):  
Shuhong Wu ◽  
Zhili Xiao ◽  
Jinlin Song ◽  
Min Li ◽  
Wenhua Li
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Regeneration ◽  
Osteogenic Differentiation ◽  
Calcium Deposition ◽  
Mineral Formation ◽  
Human Amnion ◽  
Alp Activity ◽  
Experimental Group

Background: The aim of this study is to evaluate the effects of recombinant human bone morphogenetic protein 2 (rhBMP-2), human amnion mesenchymal stem cells (hAMSCs), and nanohydroxyapatite/collagen/poly(l-lactide) (nHAC/PLA) in tissue engineering to provide potential approaches for periodontal bone regeneration. Methods: hAMSCs were isolated from discarded amniotic membrane samples and cultured in vitro. Alkaline phosphatase (ALP) staining and alizarin red staining were performed to evaluate the osteoblast (OB) differentiation ability of hAMSCs. Three groups were divided: the experimental group (cells transfected with pcDNA3.1-rhBMP-2), the blank group (cells without gene transfection), and the control group (cells transfected with empty plasmid). RT-PCR and western blot were used to examine whether rhBMP-2 has been successfully expressed. 3-(4,5)-dimethylthiahiazol(-z-y1)-3,5-di-phenytetrazo-liumromide assay (MTT) was done to detect the effect of rhBMP-2 on hAMSCs seeded on nHAC/PLA. ALP activity, mineral formation assay, calcium, phosphate and osteocalcin (OCN) content, and OCN and RUNX2 expression of hAMSCs were detected to evaluate osteogenic differentiation capability of rhBMP-2 on hAMSCs seeded on nHAC/PLA. Results: hAMSCs exhibited intense ALP staining, obvious calcium deposition, and mineralization nodules, and rhBMP-2 were highly expressed in the experimental group. The proliferation of the hAMSCs with rhBMP-2 on nHAC/PLA was significantly higher than the cells without rhBMP-2, and the cells all increased in a time-dependent manner. rhBMP-2 significantly increased the OCN and phosphate content, mineral formation, ALP activity, osteogenic biomarkers OCN, and Runx2, and decreased calcium content in hAMSCs seeded on the nHAC/PLA scaffold. Conclusions: This finding demonstrated that hAMSCs has an ideal OB differentiation ability. rhBMP-2 facilitates the proliferation and osteogenesis of hAMSCs. The nHAC/PLA could act as a good scaffold for hAMSCs seeding, proliferation, and osteogenic differentiation. The application of rhBMP-2, nHAC/PLA, and hAMSCs in tissue engineering may offer promising possibilities for periodontal bone regeneration.

Therapeutic inhibition of microRNA-34a ameliorates aortic valve calcification via modulation of Notch1-Runx2 signalling

2019 ◽  
Author(s):  
Taku Toshima ◽  
Tetsu Watanabe ◽  
Taro Narumi ◽  
Yoichiro Otaki ◽  
Tetsuro Shishido ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Locked Nucleic Acid ◽  
Calcium Deposition ◽  
Induction Medium ◽  
Mice Model ◽  
Aortic Valve Calcification ◽  
Valve Calcification ◽  
Related Transcription Factor ◽  
Pathway Inhibition ◽  
Human Aortic Valve

Abstract Aims Calcific aortic valve stenosis (CAVS) is the most common valvular heart disease and is increased with elderly population. However, effective drug therapy has not been established yet. This study aimed to investigate the role of microRNAs (miRs) in the development of CAVS. Methods and results We measured the expression of 10 miRs, which were reportedly involved in calcification by using human aortic valve tissue from patients who underwent aortic valve replacement with CAVS or aortic regurgitation (AR) and porcine aortic valve interstitial cells (AVICs) after treatment with osteogenic induction medium. We investigated whether a specific miR-inhibitor can suppress aortic valve calcification in wire injury CAVS mice model. Expression of miR-23a, miR-34a, miR-34c, miR-133a, miR-146a, and miR-155 was increased, and expression of miR-27a and miR-204 was decreased in valve tissues from CAVS compared with those from AR. Expression of Notch1 was decreased, and expression of Runt-related transcription factor 2 (Runx2) was increased in patients with CAVS compared with those with AR. We selected miR-34a among increased miRs in porcine AVICs after osteogenic treatment, which was consistent with results from patients with CAVS. MiR-34a increased calcium deposition in AVICs compared with miR-control. Notch1 expression was decreased, and Runx2 expression was increased in miR-34a transfected AVICs compared with that in miR-control. Conversely, inhibition of miR-34a significantly attenuated these calcification signals in AVICs compared with miR-control. RNA pull-down assay revealed that miR-34a directly targeted Notch1 expression by binding to Notch1 mRNA 3′ untranslated region. In wire injury CAVS mice, locked nucleic acid miR-34a inhibitor suppressed aortic velocity, calcium deposition of aortic valves, and cardiac hypertrophy, which were involved in decreased Runx2 and increased Notch1 expressions. Conclusion miR-34a plays an important role in the development of CAVS via Notch1–Runx2 signalling pathway. Inhibition of miR-34a may be the therapeutic target for CAVS.

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