ArticleJournal of molecular medicine (Berlin, Germany)2012
Rapamycin inhibits osteoclast formation in giant cell tumor of bone through the C/EBPβ - MafB axis.
Article in Journal of molecular medicine (Berlin, Germany), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 33 citations in OpenAlex.
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- Concomitant induction of SLIT3 and microRNA-218-2 in macrophages by toll-like receptor 4 activation limits osteoclast commitment.Cell communication and signaling : CCS · 2023Article
- A novel adiponectin receptor agonist (AdipoAI) ameliorates type 2 diabetes-associated periodontitis by enhancing autophagy in osteoclasts.Journal of periodontal research · 2022Article
- EZH2 Supports Osteoclast Differentiation and Bone Resorption Via Epigenetic and Cytoplasmic Targets.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2020Article
- Autophagy plays an essential role in bone homeostasis.Journal of cellular physiology · 2019Review
- PPARD is an Inhibitor of Cartilage Growth in External Ears.International journal of biological sciences · 2017Article
- Osteoclasts-Key Players in Skeletal Health and Disease.Microbiology spectrum · 2016Review
- Galectin-3 in bone tumor microenvironment: a beacon for individual skeletal metastasis management.Cancer metastasis reviews · 2016Review
- Glucose-dependent downregulation of glucagon gene expression mediated by selective interactions between ALX3 and PAX6 in mouse alpha cells.Diabetologia · 2016Article
- Rapamycin reduces severity of senile osteoporosis by activating osteocyte autophagy.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2016Article
- IL-6 and IGF-1 Signaling Within and Between Muscle and Bone: How Important is the mTOR Pathway for Bone Metabolism?Current osteoporosis reports · 2015Review
- TGR5 reduces macrophage migration through mTOR-induced C/EBPβ differential translation.The Journal of clinical investigation · 2014Article
- Regulation of monocyte differentiation by specific signaling modules and associated transcription factor networks.Cellular and molecular life sciences : CMLS · 2014Review
- The role of small molecules in musculoskeletal regeneration.Regenerative medicine · 2012Review
- CCAAT enhancer-binding proteins have long boney fingers.Journal of molecular medicine (Berlin, Germany) · 2012Article
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Giant cell tumor (GCT) of bone is a benign type of tumor, but the presence of hyperactive multinucleated giant osteoclasts cause local osteolytic lesions, increasing morbidity in patients. To specifically target hyperactive multinucleated giant osteoclasts in GCTs, one would envisage the usage of osteoclast inhibitors or genetic modulation of osteoclastogenesis. Recently, we have found that the translationally regulated balance between the transcription factor C/EBPβ long (LAP) and short (LIP) protein isoforms regulates osteoclast differentiation. Here, we report that GCTs express high levels of the LIP C/EBPβ isoform, which in mice cause giant osteoclast formation. In mice, inhibition of mTOR activity by rapamycin decreased osteoclast differentiation by shifting the alternative translation initiation of C/EBPβ isoforms towards LAP. Similarly, rapamycin treatment of GCT cell cultures derived from seven different patients strongly reduced formation of giant osteoclasts and bone resorption. This was accompanied by an increase in MafB, previously shown to be the mediator of the effect of rapamycin on osteoclast differentiation in mice. These data suggest that C/EBPβ is a determinant of giant osteoclast formation in GCT and that pharmacological adjustment of the C/EBPβ isoform ratio could serve as a potential novel therapeutic approach.
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