The Regulatory Role of GBF1 on Osteoclast Activation Through EIF2a Mediated ER Stress and Novel Marker FAM129A Induction

Wen, Cailing; Zhou, Yiming; Xu, Yanting; Tan, Huijing; Pang, Caixia; Liu, Haiqian; Liu, Kaifei; Wei, Linlin; Luo, Hongyu; Qin, Tian; He, Chonghua; Liu, Cuiling; Zhou, Chun

doi:10.3389/fcell.2021.706768

Cited by 11 publications

(11 citation statements)

References 43 publications

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“…The results are supported by the findings of Cevik et al (2020) and suggest that NIBAN1 may be involved in the decision-making process between cell survival and death in response to stressful conditions. In osteoclasts, the GBF1 knockdown, responsible for activation of the ARFs family and vesicular transport at the endoplasmic reticulum-Golgi interface, led to increased NIBAN1 , BiP, p-PERK, and p-EIF2α expression ( Wen et al, 2021 ). These genes are considered biomarkers of reticulum stress and their up-regulation seems to promote the autophagic axis of Beclin1, Atg7, p62, and LC3 ( Wen et al, 2021 ).…”

Section: Niban1 Functionsmentioning

confidence: 99%

“…In osteoclasts, the GBF1 knockdown, responsible for activation of the ARFs family and vesicular transport at the endoplasmic reticulum-Golgi interface, led to increased NIBAN1 , BiP, p-PERK, and p-EIF2α expression ( Wen et al, 2021 ). These genes are considered biomarkers of reticulum stress and their up-regulation seems to promote the autophagic axis of Beclin1, Atg7, p62, and LC3 ( Wen et al, 2021 ).…”

Section: Niban1 Functionsmentioning

confidence: 99%

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NIBAN1, Exploring its Roles in Cell Survival Under Stress Context

Diana

Carvalheira

2022

Front. Cell Dev. Biol.

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Cell survival must quickly activate specific mechanisms that enable to detect changes in the cellular microenvironment. The impact of these cell alteration has direct consequences on cellular homeostasis. Cellular stress, as well as its regulation and implication, has been studied in different pathologies. In this sense, the alteration in NIBAN1 expression seems to act in response to different cellular disturbances. Over the years, the knowledge of NIBAN1 functions has improved, demonstrating its important cell roles, favoring the cell survival under stress context. In response to the disturbances, NIBAN1 seems to be involved in the decision-making process between cell survival and death. The increase in NIBAN1 expression has been related to cellular mechanisms that seek to minimize the damage caused to cellular homeostasis. In this review, the main biological insights attributed to the NIBAN1 gene in different cellular contexts and its role as a mediator of cellular stress are discussed.

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Section: Niban1 Functionsmentioning

confidence: 99%

Section: Niban1 Functionsmentioning

confidence: 99%

NIBAN1, Exploring its Roles in Cell Survival Under Stress Context

Diana

Carvalheira

2022

Front. Cell Dev. Biol.

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“…The loss of focal adhesion of osteoclasts will lead to their inability to bind to the matrix and move normally during bone resorption, thereby accelerating bone loss. 25 Currently, there is a lack of genetic-level research on focal adhesion in OP.…”

Section: Discussionmentioning

confidence: 99%

Integration of single‐cell and RNA‐seq data to explore the role of focal adhesion‐related genes in osteoporosis

Shi,

Fu,

Mao

et al. 2024

J Cellular Molecular Medi

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Integrin‐based focal adhesion is one of the major mechanosensory in osteocytes. The aim of this study was to mine the hub genes associated with focal adhesion and investigate their roles in osteoporosis based on the data of single‐cell RNA sequencing and RNA‐sequencing. Two hub genes (FAM129A and RNF24) with the same expression trend and AUC values greater than 0.7 in both GSE56815 and GSE56116 cohorts were uncovered. The nomogram was created to predict the risk of OP based on two hub genes. Subsequently, the competing endogenous RNA network was established based on two hub genes, 14 microRNAs and five long noncoding RNAs. Meanwhile, transcription factors‐hub gene network was established based on two hub genes and 14 TFs. Finally, 73 drugs were predicted, of which there were 13 drugs targeting FAM129A and 66 drugs targeting RNF24. In both mouse and human blood samples, FAM129A expression was decreased in granulocytes and RNF24 expression was increased in monocytes. In the mouse experiment, FAM129A and anti‐RNF24 were found to partially alleviate the progression of osteoporosis. In conclusion, two hub genes related to focal adhesion were identified by combined scRNA‐seq and RNA‐seq analyses, which might supply a new insight for the treatment and evaluation of OP.

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“…Cell plates or histological sections were stained with a tartrate‐resistant acid phosphatase (TRAP) staining solution (G1492‐4 × 20 mL, Solarbio, Beijing, China) for 40 min (cell plate) or 20 min (slides) followed by hematoxylin or methyl green following the manufacturer's instructions. Positive multinucleated osteoclasts (≥3 nuclei) were observed and counted 13,33 . Immunohistochemically stained slices from the proximal epiphyses and growth plates of the proximal tibiae were analyzed 13,22 .…”

Section: Methodsmentioning

confidence: 99%

“…Positive multinucleated osteoclasts (≥3 nuclei) were observed and counted. 13,33 Immunohistochemically stained slices from the proximal epiphyses and growth plates of the proximal tibiae were analyzed. 13,22 The osteoclast numbers and osteoclast surface areas were assessed using ImageJ (USA).…”

Section: Histological Stainingmentioning

confidence: 99%

Bindarit Reduces Bone Loss in Ovariectomized Mice by Inhibiting CCL2 and CCL7 Expression via the NF‐κB Signaling Pathway

Yuan

Wang

et al. 2022

Orthopaedic Surgery

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Objective To investigate the changes in proinflammatory cytokines and chemokines, namely, C‐C motif ligand (CCL) 2 and CCL7, in postmenopausal osteoporosis (PMOP) and to develop a new drug, bindarit (Bnd), for PMOP in an ovariectomized (OVX) mouse model. Methods Bone marrow macrophages (BMMs) from the femurs of five women with PMOP and five premenopausal women without osteoporosis were detected by RNA sequencing. BMMs from mice were differentiated into osteoclasts and treated with a synthetic inhibitor of CCL2 and CCL7, Bnd, or 17 beta estradiol (E2). Mouse BMMs were differentiated into osteoclasts with or without Bnd for 7 days and analyzed by RNA sequencing. Osteoblasts of mice were induced to undergo osteoblastogenesis and treated with Bnd. OVX mice were treated with E2 or Bnd after surgery. The protein and mRNA expression of CCL2 and CCL7 was detected using immunostaining and qPCR, respectively, in OVX and aged mice and in cells cultured in vitro. Osteoclast formation was detected using a tartrate‐resistant acid phosphatase (TRAP) assay in vitro and in vivo. Alkaline phosphatase (ALP), runt‐related transcription factor 2 (Runx2) and osteocalcin (OCN) were detected using immunostaining to evaluate osteogenesis. Microcomputed tomography was conducted to analyze trabecular bone parameters, the structure model index, bone mineral density and other variables. Nuclear factor‐κB (NF‐κB) signaling pathway‐related protein phosphorylation of IKKα/β (p‐IKKα/β) and p‐NFκB p65 was examined using western blotting. Results CCL2, CCL7 and their receptor of C‐C chemokine receptor‐2 (CCR2), and the NF‐κB signaling pathway, were significantly increased in women with PMOP. CCL2 and CCL7 protein and mRNA expression was increased in OVX mice and aged female mice, but the increases were attenuated by E2 and Bnd. E2 and Bnd effectively inhibited osteoclastogenesis and the protein expression of CCL2 and CCL7 both in vitro and in vivo and reduced bone loss in OVX mice. Bnd did not affect the mineralization of osteoblasts directly in vitro but reduced bone turnover in vivo. p‐IKKα/β and p‐NFκB p65 levels were increased in BMMs of mice after differentiation into osteoclasts but were significantly decreased by Bnd. Conclusion The proinflammatory cytokines and chemokines CCL2, CCL7 and CCR2 were correlated with PMOP. Bnd attenuated the increases in CCL2 and CCL7 levels to affect osteoporosis in OVX mice via the NFκB signaling pathway. Thus, Bnd may be useful as a new therapeutic for the prevention of PMOP.

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The Regulatory Role of GBF1 on Osteoclast Activation Through EIF2a Mediated ER Stress and Novel Marker FAM129A Induction

Cited by 11 publications

References 43 publications

NIBAN1, Exploring its Roles in Cell Survival Under Stress Context

NIBAN1, Exploring its Roles in Cell Survival Under Stress Context

Integration of single‐cell and RNA‐seq data to explore the role of focal adhesion‐related genes in osteoporosis

Bindarit Reduces Bone Loss in Ovariectomized Mice by Inhibiting CCL2 and CCL7 Expression via the NF‐κB Signaling Pathway

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