Targeted Disruption of TGFBI in Mice Reveals Its Role in Regulating Bone Mass and Bone Size through Periosteal Bone Formation

Yu, Hongrun; Wergedal, Jon E.; Zhao, Yongliang; Mohan, Subburaman

doi:10.1007/s00223-012-9613-6

Cited by 32 publications

(21 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been reported that macrophages and a dendritic cell line infected with type III T. gondii expressed Irf4 mRNA at a higher level than the cells infected with type II parasites (45). Tgfbi, a secreted protein that is induced by transforming growth factor beta in various cell types, has roles in the regulation of bone mass and bone size through periosteal bone formation (46). Tgfbi has also been shown to be a tumor suppressor factor; transfection of the Tgfbi gene into tumor cells resulted in a significant reduction in tumor growth, while Tgfbi-deficient mice showed an increased incidence of spontaneous tumors (47).…”

Section: Discussionmentioning

confidence: 99%

Transcriptome Analysis of Mouse Brain Infected with Toxoplasma gondii

et al. 2013

View full text Add to dashboard Cite

c Toxoplasma gondii is an obligate intracellular parasite that invades a wide range of vertebrate host cells. Chronic infections with T. gondii become established in the tissues of the central nervous system, where the parasites may directly or indirectly modulate neuronal function. However, the mechanisms underlying parasite-induced neuronal disorder in the brain remain unclear. This study evaluated host gene expression in mouse brain following infection with T. gondii. BALB/c mice were infected with the PLK strain, and after 32 days of infection, histopathological lesions in the frontal lobe were found to be more severe than in other areas of the brain. Total RNA extracted from infected and uninfected mouse brain samples was subjected to transcriptome analysis using RNA sequencing (RNA-seq). In the T. gondii-infected mice, 935 mouse brain genes were upregulated, whereas 12 genes were downregulated. GOstat analysis predicted that the upregulated genes were primarily involved in host immune responses and cell activation. Positive correlations were found between the numbers of parasites in the infected mouse brains and the expression levels of genes involved in host immune responses. In contrast, genes that had a negative correlation with parasite numbers were predicted to be involved in neurological functions, such as small-GTPase-mediated signal transduction and vesicle-mediated transport. Furthermore, differential gene expression was observed between mice exhibiting the clinical signs of toxoplasmosis and those that did not. Our findings may provide insights into the mechanisms underlying neurological changes during T. gondii infection.T oxoplasma gondii, an obligate intracellular parasite, invades a wide variety of cells in its vertebrate hosts. The disease caused by T. gondii is usually asymptomatic but can be severe in immunosuppressed individuals, and cyst reactivation causes toxoplasmic encephalitis in AIDS patients (1). In addition, infection of nonimmune women during pregnancy can lead to congenital infection, with hydrocephaly, microcephaly, or intracerebral calcifications occurring in the fetus (2).Systemic infection by the proliferating stage of the parasite, the tachyzoite, is efficiently controlled by the cellular immune response. However, the pathogen persists in its slowly replicating stage, the bradyzoite, in tissue cysts mainly within the muscle and brain. In chronic infections, parasites within neurons can directly cause neuronal death and atrophy of neuronal processes, while inflammation via production of nitric oxide (NO) and inflammatory cytokines from microglia or immune cells may contribute to the death of neighboring neurons (3). However, the mechanisms underlying parasite-induced neuronal disorder in the brain remain unclear.In mice and rats, the specificity of behavioral modifications induced by T. gondii has been examined across a broad range of behaviors that primarily concern anxiety and learned fear in these animals (4). Recently, it has been suggested that chronic infection with T...

show abstract

Section: Discussionmentioning

confidence: 99%

Transcriptome Analysis of Mouse Brain Infected with Toxoplasma gondii

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Detailed procedures have been described previously for in vivo PIXImus measurements [23,29], for in vitro micro-CT analysis [24,30], for three-point bending [30][31][32], for real time RT-PCR [24], for serum IGF-1 assay [24,33] and for serum ALP assay [34,35]. mRNA levels in the tissue samples were measured by real time RT-PCR.…”

Section: Bone Parameter Measurements Expression Analyses and Serum Amentioning

confidence: 99%

The negative impact of traumatic brain injury (TBI) on bone in a mouse model

Watt

Mohan

2013

Brain Injury

Self Cite

View full text Add to dashboard Cite

show abstract

“…The left femur was used for bone strength testing. The following procedures were used as previously described: in vivo bone parameter measurements [28][29], serum radioimmunoassay for IGF-1 [30][31], micro-CT analysis [30][31][32], and histomorphometric analysis [32][33]. Other procedures employed are described subsequently.…”

Section: Tissue Collection and Processingmentioning

confidence: 99%

Reduced bone mass accrual in mouse model of repetitive mild traumatic brain injury

Yu¹,

Wergedal²,

Rundle³

et al. 2014

J Rehabil Res Dev

Self Cite

View full text Add to dashboard Cite

Abstract-Traumatic brain injury (TBI) can affect bone by influencing the production/actions of pituitary hormones and neuropeptides that play significant regulatory roles in bone metabolism. Previously, we demonstrated that experimental TBI exerted a negative effect on the skeleton. Since mild TBI (mTBI) accounts for the majority of TBI cases, this study was undertaken to evaluate TBI effects using a milder impact model in female mice. Repetitive mTBI caused microhemorrhaging, astrocytosis, and increased anti-inflammatory protective actions in the brain of the impacted versus control mice 2 wk after the first impact. Serum levels of growth regulating insulin-like growth factor 1 (IGF-1) were reduced by 28.9%. Bone mass was reduced significantly in total body as well as individual skeletons. Tibial total cortical density was reduced by 7.0%, which led to weaker bones, as shown by a 31.3% decrease in femoral size adjusted peak torque. A 27.5% decrease in tibial trabecular bone volume per total volume was accompanied by a 34.3% (p = 0.07) decrease in bone formation rate (BFR) per total area. Based on our data, we conclude that repetitive mTBI exerted significant negative effects on accrual of both cortical and trabecular bone mass in mice caused by a reduced BFR.

show abstract

Targeted Disruption of TGFBI in Mice Reveals Its Role in Regulating Bone Mass and Bone Size through Periosteal Bone Formation

Cited by 32 publications

References 46 publications

Transcriptome Analysis of Mouse Brain Infected with Toxoplasma gondii

Transcriptome Analysis of Mouse Brain Infected with Toxoplasma gondii

The negative impact of traumatic brain injury (TBI) on bone in a mouse model

Reduced bone mass accrual in mouse model of repetitive mild traumatic brain injury

Contact Info

Product

Resources

About