scholarly journals SARS-CoV-2 infection induces inflammatory bone loss in golden Syrian hamsters

2021 ◽  
Author(s):  
Kelvin Yeung ◽  
Wei Qiao ◽  
Hui En Lau ◽  
Hui Zhi Xie ◽  
Vincent Poon ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Metabolism ◽  
Inflammatory Diseases ◽  
Lumbar Vertebrae ◽  
Recovery Phase ◽  
Therapeutic Interventions ◽  
Limited Information ◽  
Hamster Model ◽  
Golden Syrian Hamster ◽  
Organ Systems

Abstract Extrapulmonary complications of different organ systems have been increasingly recognized in patients with severe or chronic Coronavirus Disease 2019 (COVID-19). However, limited information on the skeletal complications of COVID-19 is known, even though inflammatory diseases of the respiratory tract have been known to perturb bone metabolism and cause pathological bone loss. In this study, we characterized the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on bone metabolism in an established golden Syrian hamster model for COVID-19. SARS-CoV-2 causes significant multifocal loss of bone trabeculae in the long bones and lumbar vertebrae of all infected hamsters. The bone loss progressively worsens from the acute phase to the post-recovery phase. Mechanistically, the bone loss was associated with SARS-CoV-2-induced cytokine dysregulation which upregulates osteoclastic differentiation of monocyte-macrophage lineage. The pro-inflammatory cytokines further trigger a second wave of cytokine storm in the skeletal tissues to augment their pro-osteoclastogenesis effect. Our findings in this established hamster model suggest that pathological bone loss may be a neglected complication which warrants more extensive investigations during the long-term follow-up of COVID-19 patients. The benefits of potential prophylactic and therapeutic interventions against pathological bone loss should be further evaluated.

scholarly journals SARS-CoV-2 infection induces inflammatory bone loss in golden Syrian hamsters

2021 ◽  
Author(s):  
Wei Qiao ◽  
Hui En Lau ◽  
Huizhi Xie ◽  
Vincent K.M. Poon ◽  
Chris C.S. Chan ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Metabolism ◽  
Inflammatory Diseases ◽  
Lumbar Vertebrae ◽  
Recovery Phase ◽  
Therapeutic Interventions ◽  
Limited Information ◽  
Hamster Model ◽  
Golden Syrian Hamster ◽  
Organ Systems

Extrapulmonary complications of different organ systems have been increasingly recognized in patients with severe or chronic Coronavirus Disease 2019 (COVID-19). However, limited information on the skeletal complications of COVID-19 is known, even though inflammatory diseases of the respiratory tract have been known to perturb bone metabolism and cause pathological bone loss. In this study, we characterized the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on bone metabolism in an established golden Syrian hamster model for COVID-19. SARS-CoV-2 causes significant multifocal loss of bone trabeculae in the long bones and lumbar vertebrae of all infected hamsters. The bone loss progressively worsens from the acute phase to the post-recovery phase. Mechanistically, the bone loss was associated with SARS-CoV-2-induced cytokine dysregulation which upregulates osteoclastic differentiation of monocyte-macrophage lineage. The pro-inflammatory cytokines further trigger a second wave of cytokine storm in the skeletal tissues to augment their pro-osteoclastogenesis effect. Our findings in this established hamster model suggest that pathological bone loss may be a neglected complication which warrants more extensive investigations during the long-term follow-up of COVID-19 patients. The benefits of potential prophylactic and therapeutic interventions against pathological bone loss should be further evaluated.

scholarly journals Sex differences in lung imaging and SARS-CoV-2 antibody responses in a COVID-19 golden Syrian hamster model

2021 ◽  
Author(s):  
Santosh Dhakal ◽  
Camilo A. Ruiz-Bedoya ◽  
Ruifeng Zhou ◽  
Patrick Creisher ◽  
Jason Villano ◽  
...  
Keyword(s):  
Sex Differences ◽  
Neutralizing Antibodies ◽  
Infectious Virus ◽  
Protein S ◽  
Recovery Phase ◽  
Igg Antibodies ◽  
Infected Male ◽  
Hamster Model ◽  
Golden Syrian Hamster ◽  
Pulmonary Damage

In the ongoing coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), more severe outcomes are reported in males compared with females, including hospitalizations and deaths. Animal models can provide an opportunity to mechanistically interrogate causes of sex differences in the pathogenesis of SARS-CoV-2. Adult male and female golden Syrian hamsters (8-10 weeks of age) were inoculated intranasally with 105 TCID50 of SARS-CoV-2/USA-WA1/2020 and euthanized at several time points during the acute (i.e., virus actively replicating) and recovery (i.e., after the infectious virus has been cleared) phases of infection. There was no mortality, but infected male hamsters experienced greater morbidity, losing a greater percentage of body mass, developing more extensive pneumonia as noted on chest computed tomography, and recovering more slowly than females. Treatment of male hamsters with estradiol did not alter pulmonary damage. Virus titers in respiratory tissues, including nasal turbinates, trachea, and lungs, and pulmonary cytokine concentrations, including IFNb and TNFa, were comparable between the sexes. However, during the recovery phase of infection, females mounted two-fold greater IgM, IgG, and IgA responses against the receptor-binding domain of the spike protein (S-RBD) in both plasma and respiratory tissues. Female hamsters also had significantly greater IgG antibodies against whole inactivated SARS-CoV-2 and mutant S-RBDs, as well as virus neutralizing antibodies in plasma. The development of an animal model to study COVID-19 sex differences will allow for a greater mechanistic understanding of the SARS-CoV-2 associated sex differences seen in the human population.

scholarly journals Golden Syrian hamster as a model to study cardiovascular complications associated with SARS-CoV-2 infection

eLife ◽  
2022 ◽  
Vol 11 ◽  
Author(s):  
Zaigham Abbas Rizvi ◽  
Rajdeep Dalal ◽  
Srikanth Sadhu ◽  
Akshay Binayke ◽  
Jyotsna Dandotiya ◽  
...  
Keyword(s):  
Syrian Hamster ◽  
Troponin I ◽  
Late Phase ◽  
Cardiovascular Complications ◽  
Therapeutic Interventions ◽  
Wall Thickening ◽  
Lung Pathology ◽  
Hamster Model ◽  
Golden Syrian Hamster ◽  
Metabolic Marker

Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection in the Golden Syrian hamster causes lung pathology that resembles human coronavirus disease (COVID-19). However, extra-pulmonary pathologies associated with SARS-CoV-2 infection and post COVID sequelae remain to be understood. Here we show, using a hamster model, that the early phase of SARS-CoV-2 infection leads to an acute inflammatory response and lung pathologies, while the late phase of infection causes cardiovascular complications (CVC) characterized by ventricular wall thickening associated with increased ventricular mass/ body mass ratio and interstitial coronary fibrosis. Molecular profiling further substantiated our findings of CVC, as SARS-CoV-2-infected hamsters showed elevated levels of serum cardiac Troponin-I (cTnI), cholesterol, low-density lipoprotein and long-chain fatty acid triglycerides. Serum metabolomics profiling of SARS-CoV-2-infected hamsters identified N-acetylneuraminate, a functional metabolite found to be associated with CVC, as a metabolic marker was found to be common between SARS-CoV-2-infected hamsters and COVID-19 patients. Together, we propose hamsters as a suitable animal model to study post-COVID sequelae associated with CVC which could be extended to therapeutic interventions.

Effect of intestinal alkalinization on irinotecan (CPT-11)-induced diarrhea in the golden Syrian hamster model

2001 ◽  
Vol 120 (5) ◽  
pp. A613-A613
Author(s):  
T IKEGAMI ◽  
P LATHAM ◽  
K KOBAYASHI ◽  
K ARIMORI ◽  
B BOUSCAREL
Keyword(s):  
Syrian Hamster ◽  
Hamster Model ◽  
Golden Syrian Hamster

scholarly journals Acute motor-sensory axonal polyneuropathy variant of Guillain–Barre syndrome complicating the recovery phase of coronavirus disease 2019 infection: a case report

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Ahmed Maseh Haidary ◽  
Sarah Noor ◽  
Esmatullah Hamed ◽  
Tawab Baryali ◽  
Soma Rahmani ◽  
...  
Keyword(s):  
Recovery Phase ◽  
Sudden Onset ◽  
Therapeutic Interventions ◽  
Guillain Barre Syndrome ◽  
The Novel ◽  
Case Presentation ◽  
Progressive Muscle Weakness ◽  
Guillain Barré Syndrome ◽  
Novel Coronavirus ◽  
Guillain Barré

Abstract Introduction The novel coronavirus, since its first identification in China, in December 2019, has shown remarkable heterogeneity in its clinical behavior. It has affected humans on every continent. Clinically, it has affected every organ system. The outcome has also been variable, with most of the older patients showing grave outcomes as compared with the younger individuals. Here we present a rare and severe variant of Guillain–Barre syndrome that complicated the disease in recovery phase. Case presentation A 60-year-old Afghan man, who had been recovering from symptoms related to novel coronavirus associated disease, presented with sudden onset of progressive muscle weakness and oxygen desaturation. Electrophysiological workup confirmed the diagnosis of Guillain–Barre syndrome, and early institution of intravenous immunoglobulin resulted in complete resolution. Conclusion Guillain–Barre syndrome has recently been reported in many patients diagnosed with novel coronavirus associated disease. While clinical suspicion is mandatory to guide towards an effective diagnostic workup, early diagnosis of this complication and timely institution of therapeutic interventions are indispensable and lifesaving.

scholarly journals FRI0373 ASSOCIATIONS OF VASCULAR PATHOPHYSIOLOGY AND BONE METABOLISM IN ANTI-TNF- TREATED RHEUMATOID ARTHRITIS AND ANKYLOSING SPONDYLITIS PATIENTS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 783.2-784
Author(s):  
M. Czókolyová ◽  
K. Gulyás ◽  
Á. Horváth ◽  
E. Végh ◽  
Z. Pethö ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Ankylosing Spondylitis ◽  
Bone Loss ◽  
Bone Metabolism ◽  
Certolizumab Pegol ◽  
Univariate Analysis ◽  
Inflammatory Rheumatic Diseases ◽  
Ageing Population ◽  
Research Support ◽  
Vascular Markers

Background:Cardiovascular (CV) disease and osteoporosis (OP) have become increasing challenges in the ageing population, even more in patients with inflammatory rheumatic diseases, such as rheumatoid arthritis (RA) and spondyloarthropathies. Both RA and ankylosing spondylitis (AS) have been associated with generalized and localized bone loss, accelerated atherosclerosis, increased CV morbidity and mortality.Objectives:Bone and vascular biomarkers and parameters along with the effect of one-year anti-TNF therapy on these markers were assessed in order to determine correlations between vascular pathophysiology and bone metabolism in RA and AS.Methods:Fifty-three patients including 36 RA patients treated with etanercept (ETN) or certolizumab pegol (CZP) and 17 AS patients treated with ETN were included in a 12-month follow-up study. Bone and vascular markers were assessed by ELISA. Bone density was assessed by DXA and quantitative CT (QCT). Flow-mediated vasodilation (FMD), common carotid intima-media thickness (ccIMT) and pulse-wave velocity (PWV) were assessed by ultrasound. The effects of vascular markers on bone and bone effects on vasculature undergone statistical analysis.Results:Serum levels of vascular endothelial growth factor (VEGF), PDGF-BB, angiopoietin 2 (Ang2) and cathepsin K (CathK) decreased, procollagen type 1 N-propeptide (P1NP) and sclerostin (SOST) levels increased, soluble receptor activator nuclear kappa B ligand (sRANKL) and osteoprotegerin (OPG) levels showed no differences. When bone and vascular markers were correlated with each other, at baseline, OPG correlated with Ang2 and adiponectin. SOST correlated positively with ccIMT. DXA L2-4 BMD, DXA L1 BMD and DXA femoral neck (FN) BMD correlated with FMD and CRP. QCT trabecular BMD correlated with ccIMT and PON1. According to the univariate analysis, FMD correlated with OPG, ccIMT correlated with SOST and QCT trabecular BMD. Ang1, Ang2 and PDGF-BB showed correlation with Dickkopf-1 (DKK1). Ang2 also correlated with OPG. As suggested by the multivariate analysis, OPG determined FMD; DKK1 was an independent predictor of Ang1, Ang2 and PDGF-BB. OPG was a predictor of Ang2.Conclusion:In our study of anti-TNF treated RA and AS patients, vascular and bone parameters showed numerous correlations. The therapy was clinically effective, it halted further bone loss over 1 year and reduced the production of angiogenic markers.Acknowledgments:This research was supported by an investigator-initiated research grant from Pfizer.Disclosure of Interests:Monika Czókolyová: None declared, Katalin Gulyás: None declared, Ágnes Horváth: None declared, Edit Végh: None declared, Zsófia Pethö: None declared, Szilvia Szamosi: None declared, Attila Hamar: None declared, Anita Pusztai: None declared, Emese Balogh: None declared, Nóra Bodnár: None declared, Levente Bodoki: None declared, Agnes Szentpetery: None declared, Harjit Pal Bhattoa: None declared, György Kerekes: None declared, Katalin Hodosi: None declared, Andrea Domjan: None declared, Sándor Szántó: None declared, Gabriella Szücs: None declared, Hennie Raterman Grant/research support from: UCB, Consultant of: Abbvie, Amgen, Bristol-Myers Sqibb, Cellgene and Sanofi Genzyme, WIllem Lems Grant/research support from: Pfizer, Consultant of: Lilly, Pfizer, Zoltán Szekanecz Grant/research support from: Pfizer, UCB, Consultant of: Sanofi, MSD, Abbvie, Pfizer, Roche, Novertis, Lilly, Gedeon Richter, Amgen

scholarly journals Dietary Salt Accelerates Orthodontic Tooth Movement by Increased Osteoclast Activity

2021 ◽  
Vol 22 (2) ◽  
pp. 596
Author(s):  
Agnes Schröder ◽  
Joshua Gubernator ◽  
Alexandra Leikam ◽  
Ute Nazet ◽  
Fabian Cieplik ◽  
...  
Keyword(s):  
Bone Density ◽  
Bone Loss ◽  
Bone Metabolism ◽  
Tooth Movement ◽  
Orthodontic Tooth Movement ◽  
Dietary Salt ◽  
Osteoclast Activity ◽  
Salt Uptake ◽  
Periodontal Bone Loss ◽  
The Impact

Dietary salt uptake and inflammation promote sodium accumulation in tissues, thereby modulating cells like macrophages and fibroblasts. Previous studies showed salt effects on periodontal ligament fibroblasts and on bone metabolism by expression of nuclear factor of activated T-cells-5 (NFAT-5). Here, we investigated the impact of salt and NFAT-5 on osteoclast activity and orthodontic tooth movement (OTM). After treatment of osteoclasts without (NS) or with additional salt (HS), we analyzed gene expression and the release of tartrate-resistant acid phosphatase and calcium phosphate resorption. We kept wild-type mice and mice lacking NFAT-5 in myeloid cells either on a low, normal or high salt diet and inserted an elastic band between the first and second molar to induce OTM. We analyzed the expression of genes involved in bone metabolism, periodontal bone loss, OTM and bone density. Osteoclast activity was increased upon HS treatment. HS promoted periodontal bone loss and OTM and was associated with reduced bone density. Deletion of NFAT-5 led to increased osteoclast activity with NS, whereas we detected impaired OTM in mice. Dietary salt uptake seems to accelerate OTM and induce periodontal bone loss due to reduced bone density, which may be attributed to enhanced osteoclast activity. NFAT-5 influences this reaction to HS, as we detected impaired OTM and osteoclast activity upon deletion.

Role of endogenous regucalcin in bone metabolism: Bone loss is induced in regucalcin transgenic rats

2002 ◽  
Author(s):  
Masayoshi Yamaguchi ◽  
H. Misawa ◽  
S. Uchiyama ◽  
Y. Morooka ◽  
Y. Tsurusaki
Keyword(s):  
Bone Loss ◽  
Bone Metabolism ◽  
Transgenic Rats

Nuclear receptor Nur77: its role in chronic inflammatory diseases

2021 ◽  
Author(s):  
Sanne C. Lith ◽  
Carlie J.M. de Vries
Keyword(s):  
Nuclear Receptor ◽  
Inflammatory Disease ◽  
Inflammatory Responses ◽  
Current Knowledge ◽  
Inflammatory Diseases ◽  
Cell Types ◽  
Experimental Models ◽  
Therapeutic Interventions ◽  
Alternative Mechanism ◽  
Signaling Complex

Abstract Nur77 is a nuclear receptor that has been implicated as a regulator of inflammatory disease. The expression of Nur77 increases upon stimulation of immune cells and is differentially expressed in chronically inflamed organs in human and experimental models. Furthermore, in a variety of animal models dedicated to study inflammatory diseases, changes in Nur77 expression alter disease outcome. The available studies comprise a wealth of information on the function of Nur77 in diverse cell types and tissues. Negative cross-talk of Nur77 with the NFκB signaling complex is an example of Nur77 effector function. An alternative mechanism of action has been established, involving Nur77-mediated modulation of metabolism in macrophages as well as in T cells. In this review, we summarize our current knowledge on the role of Nur77 in atherosclerosis, inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, and sepsis. Detailed insight in the control of inflammatory responses will be essential in order to advance Nur77-targeted therapeutic interventions in inflammatory disease.

scholarly journals Gallbladder-derived surfactant protein D regulates gut commensal bacteria for maintaining intestinal homeostasis

2017 ◽  
Vol 114 (38) ◽  
pp. 10178-10183 ◽  
Author(s):  
Hana Sarashina-Kida ◽  
Hideo Negishi ◽  
Junko Nishio ◽  
Wataru Suda ◽  
Yuki Nakajima ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Local Environment ◽  
Surfactant Protein ◽  
Commensal Bacteria ◽  
Intestinal Lumen ◽  
Surfactant Protein D ◽  
Organ Systems ◽  
Notable Increase ◽  
Health And Disease ◽  
Deficient Mice

The commensal microbiota within the gastrointestinal tract is essential in maintaining homeostasis. Indeed, dysregulation in the repertoire of microbiota can result in the development of intestinal immune–inflammatory diseases. Further, this immune regulation by gut microbiota is important systemically, impacting health and disease of organ systems beyond the local environment of the gut. What has not been explored is how distant organs might in turn shape the microbiota via microbe-targeted molecules. Here, we provide evidence that surfactant protein D (SP-D) synthesized in the gallbladder and delivered into intestinal lumen binds selectively to species of gut commensal bacteria. SP-D–deficient mice manifest intestinal dysbiosis and show a susceptibility to dextran sulfate sodium-induced colitis. Further, fecal transfer from SP-D–deficient mice to wild-type, germ-free mice conveyed colitis susceptibility. Interestingly, colitis caused a notable increase inSftpdgene expression in the gallbladder, but not in the lung, via the activity of glucocorticoids produced in the liver. These findings describe a unique mechanism of interorgan regulation of intestinal immune homeostasis by SP-D with potential clinical implications such as cholecystectomy.

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