ArticleNature medicine2009
Coordination of PGC-1beta and iron uptake in mitochondrial biogenesis and osteoclast activation.
Article in Nature medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 239 papers.
What it found
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Who cites it
239 citing papers in PubMed, 394 citations in OpenAlex.
- Thromboxane A2 receptor signalling amplifies osteoclastogenesis in rheumatoid arthritis through ACSL1 associated mitochondrial oxidative metabolism.Nature communications · 2026Article
- Mitochondrial Quality Control in Degenerative Musculoskeletal Diseases: Signaling Networks and Therapeutic Landscapes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- A Novel Reactive Oxygen Species-Responsive Bone-Targeted Nanoplatform Based on Cloperastine Attenuates Ovariectomy-Induced Bone Loss by Inhibiting Osteoclast Oxidative Phosphorylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Protein acylation and bone metabolism: bidirectional crosstalk linking metabolic reprogramming to skeletal homeostasis.Journal of molecular histology · 2026Review
- Integrated metabolomic and gut microbiota analyses reveal TCA cycle dysfunction in broiler skeletal disorders and the protective effect of L‑malic acid.Journal of animal science and biotechnology · 2026Article
- OXR1 is a dual redox-mitochondrial checkpoint governing osteoclast differentiation and bone loss in an osteoporosis mouse model.Nature communications · 2026Article
- Angiogenin mediates cell-cell fusion as a mitochondrial RNA processing enzyme.Bone research · 2026Article
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- Hells protects mitochondrial integrity via Nr2f2 suppression during osteoclast differentiation.Cell communication and signaling : CCS · 2026Article
- m6A RNA modifications in neurosystem genes as early markers for osteoporosis with iron accumulation.Molecular biology reports · 2026Article
- The osteoclast intracellular environment fosters bacterial growth duringbioRxiv : the preprint server for biology · 2026Article
- Punicalagin with anti-inflammatory activities affects Brd-4 mediated chromatin remodeling for attenuating inflammatory osteolysis.Scientific reports · 2026Article
- Role of mitochondrial dysfunction in muscle wasting in cancer cachexia: a narrative review.Journal of translational medicine · 2026Review
- Association of serum ferritin with bone turnover markers and bone mineral density in children and adolescents: Finding from NHANES 1999-2002.The Journal of international medical research · 2026Article
- The Interplay Between Bone Biology and Iron Metabolism: Molecular Mechanisms and Clinical Implications.Biomedicines · 2026Review
- Iron overload disrupts bone homeostasis via TfR1-dependent ferroptosis and cGAS/STING-driven pyroptosis in pyogenic spondylitis.Frontiers in immunology · 2026Article
- Targeting ferroptosis in osteoporosis: mechanisms and natural products therapies.Frontiers in pharmacology · 2026Review
- Mitigating mitochondrial dysfunction: a novel strategy for Chinese botanical drugs against osteoporosis.Frontiers in pharmacology · 2026Review
- Single-cell landscape of lymphoid and myeloid heterogeneity across type-stratified craniofacial lesions in polyostotic fibrous dysplasia.Frontiers in immunology · 2026Article
179 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 8 institutions in 3 countries.
Funding
Abstract
Osteoclasts are acid-secreting polykaryons that have high energy demands and contain abundant mitochondria. How mitochondrial biogenesis is integrated with osteoclast differentiation is unknown. We found that the transcription of Ppargc1b, which encodes peroxisome proliferator-activated receptor-gamma coactivator 1beta (PGC-1beta), was induced during osteoclast differentiation by cAMP response element-binding protein (CREB) as a result of reactive oxygen species. Knockdown of Ppargc1b in vitro inhibited osteoclast differentiation and mitochondria biogenesis, whereas deletion of the Ppargc1b gene in mice resulted in increased bone mass due to impaired osteoclast function. We also observed defects in PGC-1beta-deficient osteoblasts. Owing to the heightened iron demand in osteoclast development, transferrin receptor 1 (TfR1) expression was induced post-transcriptionally via iron regulatory protein 2. TfR1-mediated iron uptake promoted osteoclast differentiation and bone-resorbing activity, associated with the induction of mitochondrial respiration, production of reactive oxygen species and accelerated Ppargc1b transcription. Iron chelation inhibited osteoclastic bone resorption and protected against bone loss following estrogen deficiency resulting from ovariectomy. These data establish mitochondrial biogenesis orchestrated by PGC-1beta, coupled with iron uptake through TfR1 and iron supply to mitochondrial respiratory proteins, as a fundamental pathway linked to osteoclast activation and bone metabolism.
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Registered trials
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.