Tauroursodeoxycholic acid attenuates inorganic phosphate-induced osteoblastic differentiation and mineralization in NIH3T3 fibroblasts by inhibiting the ER stress response PERK-eIF2α-ATF4 pathway

Liu, Fang; Cui, Yazhou; Ge, Pinglan; Luan, Jing; Zhou, Xiaoyan; Han, Jinxiang

doi:10.5582/ddt.2015.01008

Cited by 16 publications

(3 citation statements)

References 34 publications

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“… 36 , 37 Tm and Tg both promoted reprogramming at proper concentrations but suppressed reprogramming at high concentrations owing to impaired cell survival (Figure S3 A,B). However, when we tried an ER stress inhibitor, tauroursodeoxycholic acid (TUDCA), which functions as a chemical chaperone, reduces stress‐induced aggregation of proteins and inhibits the PERK pathway to prevent unfolded protein response (UPR) dysfunction, 38 , 39 we found that it negligibly affected reprogramming efficiency (Figure S3 B). Thus, we speculated that the response to ER stress can promote reprogramming, and it may not through PERK pathway.…”

Section: Resultsmentioning

confidence: 99%

Surf4 facilitates reprogramming by activating the cellular response to endoplasmic reticulum stress

et al. 2021

Cell Proliferation

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Objectives: Maternal factors that are enriched in oocytes have attracted great interest as possible key factors in somatic cell reprogramming. We found that surfeit locus protein 4 (Surf4), a maternal factor, can facilitate the generation of induced pluripotent stem cells (iPSCs) previously, but the mechanism remains elusive. Materials and Methods:In this study, we investigated the function and mechanism of Surf4 in somatic cell reprogramming using a secondary reprogramming system.Alkaline phosphatase (AP) staining, qPCR and immunofluorescence (IF) staining of expression of related markers were used to evaluate efficiency of iPSCs derived from mouse embryonic fibroblasts. Embryoid body and teratoma formation assays were performed to evaluate the differentiation ability of the iPSC lines. RNA-seq, qPCR and western blot analysis were applied to validate the downstream targets of Surf4.Results: Surf4 can significantly facilitate the generation of iPSCs in a proliferationindependent manner. When co-expressed with Oct4, Sox2, Klf4 and c-Myc (OSKM), Surf4 can activate the response to endoplasmic reticulum (ER) stress at the early stage of reprogramming. We further demonstrated that Hspa5, a major ER chaperone, and the active spliced form of Xbp1 (sXbp1), a major mediator of ER stress, can mimic the effects of Surf4 on somatic cell reprogramming. Concordantly, blocking the unfolded protein response compromises the effect of Surf4 on reprogramming.

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Section: Resultsmentioning

confidence: 99%

Surf4 facilitates reprogramming by activating the cellular response to endoplasmic reticulum stress

et al. 2021

Cell Proliferation

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“…In addition, TUDCA at 100 nM and 1 µM concentrations improved bone mineralization and 1 mM TUDCA protected osteoblasts from MP-induced apoptosis. TUDCA has been proven to inhibit endoplasmic reticulum (ER) stress, which is associated with osteoclastogenesis [ 20 ]. An inducer of ER stress (thapsigargin) was demonstrated to decrease osteoclast formation from RAW264.7 macrophages [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Potential of Tauroursodeoxycholic Acid for the Treatment of Osteoporosis

Ahn

Kim

Joshi

et al. 2020

IJMS

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Tauroursodeoxycholic acid (TUDCA) is a US FDA-approved hydrophilic bile acid for the treatment of chronic cholestatic liver disease. In the present study, we investigate the effects of TUDCA on the proliferation and differentiation of osteoblasts and its therapeutic effect on a mice model of osteoporosis. Following treatment with different concentrations of TUDCA, cell viability, differentiation, and mineralization were measured. Three-month-old female C57BL/6 mice were randomly divided into three groups (n = 8 mice per group): (i) normal mice as the control group, (ii) ovariectomy (OVX) group (receiving phosphate-buffered saline (PBS) treatment every other day for 4 weeks), and (iii) OVX group with TUDCA (receiving TUDCA treatment every other day for 4 weeks starting 6 weeks after OVX). At 11 weeks post-surgery, serum levels of procollagen type I N-terminal propeptides (PINP) and type I collagen crosslinked C-telopeptides (CTX) were measured, and all mice were sacrificed to examine the distal femur by micro-computed tomography (CT) scans and histology. TUDCA (100 nM, 1 µM) significantly increased the proliferation and viability of osteoblasts and osteoblast differentiation and mineralization when used in vitro. Furthermore, TUDCA neutralized the detrimental effects of methylprednisolone (methylprednisolone-induced osteoblast apoptosis). In the TUDCA treatment group the PINP level was higher and the CTX level was lower, but these levels were not significantly different compared to the PBS treatment group. Micro-CT and histology showed that the TUDCA treatment group preserved more trabecular structures in the distal femur compared to the PBS treatment group. In addition, the TUDCA treatment group increased the percentage bone volume with respect to the total bone volume, bone mineral density, and mice distal femur trabeculae compared with the PBS treatment group. Taken together, our findings suggest that TUDCA may provide a favorable effect on bones and could be used for the prevention and treatment of osteoporosis.

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“…For those parasites that are more sensitive to ER stress inducers than their hosts, it is necessary to explore the appropriate concentration of these inducers. TUDCA, a bile salt and chemical chaperone used to treat biliary cirrhosis clinically ( Lazaridis et al, 2001 ), partially inhibits ER stress by lowering the levels of PERK, Bip ( Malo et al, 2010 ; Liu et al, 2015 ; Li et al, 2019 ). Thus, TUDCA may be an alternative therapy for parasitosis.…”

Section: The Upr In Parasites Suggests Potential Drug Targets For Inhibiting the Survival And Development Of Parasitesmentioning

confidence: 99%

Endoplasmic Reticulum Stress, a Target for Drug Design and Drug Resistance in Parasitosis

Peng

Fang

et al. 2021

Front. Microbiol.

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Endoplasmic reticulum stress (ER stress) can be induced when cellular protein homeostasis is damaged, and cells can activate the unfolded protein response (UPR) to restore protein homeostasis or induce cell death to facilitate the survival of the whole system. Globally, parasites are a constant threat to human health and are therefore considered a serious public health problem. Parasitic infection can cause ER stress in host cells, and parasites also possess part or all of the UPR under ER stress conditions. In this review, we aim to clarify the role of ER stress pathways and related molecules in parasites for their survival and development, the pathogenesis of parasitosis in hosts, and the artemisinin resistance of Plasmodium, which provides some potential drug design targets to inhibit survival of parasites, relieves pathological damage of parasitosis, and solves the problem of artemisinin resistance.

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Tauroursodeoxycholic acid attenuates inorganic phosphate-induced osteoblastic differentiation and mineralization in NIH3T3 fibroblasts by inhibiting the ER stress response PERK-eIF2α-ATF4 pathway

Cited by 16 publications

References 34 publications

Surf4 facilitates reprogramming by activating the cellular response to endoplasmic reticulum stress

Surf4 facilitates reprogramming by activating the cellular response to endoplasmic reticulum stress

Therapeutic Potential of Tauroursodeoxycholic Acid for the Treatment of Osteoporosis

Endoplasmic Reticulum Stress, a Target for Drug Design and Drug Resistance in Parasitosis

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