Zika virus infection perturbs osteoblast function

Mumtaz, Noreen; Koedam, Marijke; Doel, Petra B. van den; Leeuwen, Johannes P.T.M. van; Eerden, Bram C. J. van der; Rockx, Barry

doi:10.1038/s41598-018-35422-3

Cited by 13 publications

(51 citation statements)

References 26 publications

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“…BMMSC-derived osteogenic differentiation is essential for bone homeostasis (18–20). Recent studies show that viral infection can affect the function of BMMSCs and BMMSC-derived osteogenic cells (21, 22). However, to date, it is unknown whether alphaviruses can infect BMMSCs and disrupt osteogenic cell function.…”

Section: Resultsmentioning

confidence: 99%

“…Osteogenic differentiation of BMMSCs plays an important role in bone homeostasis (18–20). In addition, viral infection have been associated with altered function of BMMSC-derived osteogenic cells (21). Therefore, we next investigated the fate of CHIKV-infected, differentiated BMMSCs.…”

Section: Resultsmentioning

confidence: 99%

“…Prior studies have shown viral infection of osteogenic cells causes impaired ALP activity during differentiation (21). To examine the effect of CHIKV infection on ALP activity, BMMSCs were infected as previously outlined (Fig 1).…”

Section: Resultsmentioning

confidence: 99%

“…These cells can secrete and respond to different signaling molecules and undergo osteogenic differentiation thereby playing an essential role in bone homeostasis (18, 25). Previous studies have shown that virus infection can affect functions of BMMSCs (21, 22, 26), but it is unclear whether BMMSCs are susceptible to alphavirus infection.…”

Section: Discussionmentioning

confidence: 99%

“…The osteogenic differentiation of BMMSCs is important for bone-remodeling, and the inability of BMMSCs to differentiate into the osteogenic lineage may lead to an imbalance in bone remodeling and eventually bone loss (18–20). A few studies have shown that virus infection of BMMSCs can affect the properties and function of these cells (21, 22).…”

Section: Introductionmentioning

confidence: 99%

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Chikungunya virus infection impairs osteogenic differentiation of bone marrow-derived mesenchymal stem cells

Roy

Shi

Duan

et al. 2019

Preprint

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20Chikungunya virus (CHIKV) is a positive-sense, single-stranded RNA virus, 21 belonging to the genus alphavirus in the family Togaviridae. The virus is spread by the 22 Importance 43Although studies have shown association of bone pathology and CHIKV 44 infection, the pathogenesis of infection causing altered bone homeostasis is not fully 45 understood. Here, we demonstrate for the first time that BMMSCs are susceptible to 46 CHIKV infection.Furthermore, we observe that infection causes disruption in the 47 function of BMMSC-derived osteogenic cells. Impaired function of these osteogenic 48 cells will likely lead to a disruption in bone homeostasis and in part, provides a 49 mechanism for the observed bone pathology associated with CHIKV pathogenesis. 50 Keywords 51 Chikungunya virus, mesenchymal stem cells, osteogenic differentiation 52 53 54 55 56 57 58 59 60 61 62 63

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Chikungunya virus infection impairs osteogenic differentiation of bone marrow-derived mesenchymal stem cells

Roy

Shi

Duan

et al. 2019

Preprint

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Zika virus alters osteogenic lineage progression of human mesenchymal stromal cells

Mumtaz

Dudakovic

Nair

et al. 2022

Journal Cellular Physiology

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Arboviruses target bone forming osteoblasts and perturb bone remodeling via paracrine factors. We previously reported that Zika virus (ZIKV) infection of earlystage human mesenchymal stromal cells (MSCs) inhibited the osteogenic lineage commitment of MSCs. To understand the physiological interplay between bone development and ZIKV pathogenesis, we employed a primary in vitro model to examine the biological responses of MSCs to ZIKV infection at different stages of osteogenesis. Precommitted MSCs were infected at the late stage of osteogenic stimulation (Day 7) with ZIKV (multiplicity of infection of 5). We observe that MSCs infected at the late stage of differentiation are highly susceptible to ZIKV infection similar to previous observations with early stage infected MSCs (Day 0). However, in contrast to ZIKV infection at the early stage of differentiation, infection at a later stage significantly elevates the key osteogenic markers and calcium content.Comparative RNA sequencing (RNA-seq) of early and late stage infected MSCs reveals that ZIKV infection alters the mRNA transcriptome during osteogenic induction of MSCs (1251 genes). ZIKV infection provokes a robust antiviral response at both stages of osteogenic differentiation as reflected by the upregulation of interferon responsive genes (n > 140). ZIKV infection enhances the expression of immune-related genes in early stage MSCs while increasing cell cycle genes in late stage MSCs. Remarkably, ZIKA infection in early stage MSCs also activates lipid metabolism-related pathways. In conclusion, ZIKV infection has differentiation stage-dependent effects on MSCs and this mechanistic understanding may permit the development of new therapeutic or preventative measures for bone-related effects of ZIKV infection.

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