ArticleAnnals of the New York Academy of Sciences2016
Enhanced osteoclastogenesis by mitochondrial retrograde signaling through transcriptional activation of the cathepsin K gene.
Article in Annals of the New York Academy of Sciences, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- From force to resorption: mechanotransduction, osteoclasts, prevention.Progress in orthodontics · 2026Review
- Protein interactions, network pharmacology, and machine learning work together to predict genes linked to mitochondrial dysfunction in hypertrophic cardiomyopathy.Scientific reports · 2025Article
- Basic biology and roles of CEBPD in cardiovascular disease.Cell death discovery · 2025Review
- The feasibility of targeting macrophage for disease treatment: roles of CEBPD.Frontiers in immunology · 2025Review
- Single-cell multi-omics identify novel regulators required for osteoclastogenesis during aging.iScience · 2024Article
- Strategies of Macrophages to Maintain Bone Homeostasis and Promote Bone Repair: A Narrative Review.Journal of functional biomaterials · 2022Review
- Cytochrome c oxidase dysfunction enhances phagocytic function and osteoclast formation in macrophages.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Reactive Oxygen Species in Osteoclast Differentiation and Possible Pharmaceutical Targets of ROS-Mediated Osteoclast Diseases.International journal of molecular sciences · 2019Review
- Paeoniflorin ameliorates collagen-induced arthritis via suppressing nuclear factor-κB signalling pathway in osteoclast differentiation.Immunology · 2018Article
- Chronic Psychosocial Stress Impairs Bone Homeostasis: A Study in the Social Isolation Reared Rat.Frontiers in pharmacology · 2016Article
- Functional osteoclastogenesis: the baseline variability in blood donor precursors is not associated with age and gender.Oncotarget · 2015Article
- Hypoxic regulation of osteoclast differentiation and bone resorption activity.Hypoxia (Auckland, N.Z.) · 2015Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Mitochondrial dysfunction has emerged as an important factor in wide ranging human pathologies. We have previously defined a retrograde signaling pathway that originates from dysfunctional mitochondria (Mt-RS) and causes a global nuclear transcriptional reprograming as its end point. Mitochondrial dysfunction causing disruption of mitochondrial membrane potential and consequent increase in cytosolic calcium [Ca(2) ](c) activates calcineurin and the transcription factors NF-κB, NFAT, CREB, and C/EBPδ. In macrophages, this signaling complements receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclastic differentiation. Here, we show that the Mt-RS activated transcriptional coactivator heterogeneous ribonucleoprotein A2 (hnRNP A2) is induced by hypoxia in murine macrophages. We demonstrate that the cathepsin K gene (Ctsk), one of the key genes upregulated during osteoclast differentiation, is transcriptionally activated by Mt-RS factors. HnRNP A2 acts as a coactivator with nuclear transcription factors, cRel, and C/EBPδ for Ctsk promoter activation under hypoxic conditions. Notably, our study shows that hypoxia-induced activation of the stress target factors mediates effects similar to that of RANKL with regard to Ctsk activation. We therefore suggest that mitochondrial dysfunction and activation of Mt-RS, induced by various pathophysiologic conditions, is a potential risk factor for osteoclastogenesis and bone loss.
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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.