ArticleCell death & disease2014
Deficiency of osteoblastic Arl6ip5 impaired osteoblast differentiation and enhanced osteoclastogenesis via disturbance of ER calcium homeostasis and induction of ER stress-mediated apoptosis.
Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 36 citations in OpenAlex.
- Deoxycholic Acid, a Metabolite of Circulating Bile Acids, and Coronary Artery Vascular Calcification in CKD.American journal of kidney diseases : the official journal of the National Kidney Foundation · 2018Trial
- Lineage-Dependent Regulation of Glutathione Homeostasis by EAAC1 and GTRAP3-18 During Differentiation of Mesenchymal Stem Cells into Neuron-like Cells.International journal of molecular sciences · 2026Article
- Screening and validation of ZFYVE27 as a potential diagnostic biomarker for osteoporosis via integrative bioinformatics and machine learning approaches.Frontiers in immunology · 2026Article
- Stage-dependent endoplasmic reticulum homeostasis in osteogenic differentiation.Frontiers in cell and developmental biology · 2026Review
- Prediction of the Prognosis and Treatment Responses Based on the Characteristics of Disulfidptosis-Related Genes in Patients with Cervical Squamous Cell Carcinoma and Endocervical AdenocarcinomaEndocrine, metabolic & immune disorders drug targets · 2026Article
- ADP ribosylation factor-like GTPase 6-interacting protein 5 (Arl6IP5) is an ER membrane-shaping protein that modulates ER-phagy.The Journal of biological chemistry · 2025Article
- A novel ER stress regulator ARL6IP5 induces reticulophagy to ameliorate the prion burden.Autophagy · 2025Article
- ER Stress, the Unfolded Protein Response and Osteoclastogenesis: A Review.Biomolecules · 2023Review
- Metformin reverses oxidative stress‑induced mitochondrial dysfunction in pre‑osteoblasts via the EGFR/GSK‑3β/calcium pathway.International journal of molecular medicine · 2023Article
- Tanshinone IIA attenuates valvular interstitial cells' calcification induced by oxidized low density lipoprotein via reducing endoplasmic reticulum stress.Open medicine (Warsaw, Poland) · 2023Article
- Transcriptional signatures of the BCL2 family for individualized acute myeloid leukaemia treatment.Genome medicine · 2022Article
- ARL6IP5 reduces cisplatin-resistance by suppressing DNA repair and promoting apoptosis pathways in ovarian carcinoma.Cell death & disease · 2022Article
- Lansoprazole-induced osteoporosis via the IP3R- and SOCE-mediated calcium signaling pathways.Molecular medicine (Cambridge, Mass.) · 2022Article
- RRBP1 depletion of bone metastatic cancer cells contributes to enhanced expression of the osteoblastic phenotype.Frontiers in oncology · 2022Article
- Palmitoylated small GTPase ARL15 is translocated within Golgi network during adipogenesis.Biology open · 2021Article
- Bone alterations in inflammatory bowel diseases.World journal of clinical cases · 2019Review
- The Best for the Most Important: Maintaining a Pristine Proteome in Stem and Progenitor Cells.Stem cells international · 2019Review
- Oestrogen retains human periodontal ligament stem cells stemness in long-term culture.Cell proliferation · 2018Article
- Transcription Factor C/EBP Homologous Protein in Health and Diseases.Frontiers in immunology · 2017Review
- Porcine placenta hydrolysates enhance osteoblast differentiation through their antioxidant activity and effects on ER stress.BMC complementary and alternative medicine · 2016Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
ADP-ribosylation-like factor 6 interacting protein 5 (Arl6ip5), which belongs to the prenylated rab-acceptor-family, has an important role in exocytic protein trafficking, glutathione metabolism and involves in cancer progression. However, its expression pattern and functional role in bone are unknown. Here we demonstrate that Arl6ip5 knock-out mice (Arl6ip5 (Δ2/Δ2)) show marked decrease of bone mineral density, trabecular bone volume and trabecular thickness. Histomorphometric studies reveal that bone formation parameters are decreased but bone resorption parameters and mRNA level of osteoclast-specific markers are increased in Arl6ip5(Δ2/Δ2) mice. In osteoblast, we demonstrate that Arl6ip5 abundantly expresses in osteoblastic cells and is regulated by bone metabolism-related hormones and growth factors. In vitro analysis reveals that osteoblast proliferation and differentiation are impaired in Arl6ip5 knocked-down and deficient primary osteoblast. Arl6ip5 is also found to function as an ER calcium regulator and control calmodulin signaling for osteoblast proliferation. Moreover, Arl6ip5 insufficiency in osteoblast induces ER stress and enhances ER stress-mediated apoptosis. CCAAT/enhancer-binding protein homologous protein (Chop) is involved in the regulation of apoptosis and differentiation in Arl6ip5 knocked-down osteoblasts. For osteoclastogenesis, Arl6ip5 insufficiency in osteoclast precursors has no effect on osteoclast formation. However, knocked-down osteoblastic Arl6ip5 induces receptor activator of nuclear factor-κB ligand (RANKL) expression and enhances osteoclastogenesis. In addition, ER stress and Chop are involved in the RANKL expression in Arl6ip5 knocked-down osteoblasts. In conclusion, we demonstrate that Arl6ip5 is a novel regulator of bone formation in osteoblasts.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.