ArticleNature metabolism2024
The serine synthesis pathway drives osteoclast differentiation through epigenetic regulation of NFATc1 expression.
Article in Nature metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 42 citations in OpenAlex.
- 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
- Glucose metabolism in osteoporosis: A potential therapeutic target (Review).International journal of molecular medicine · 2026Review
- Disulfidptosis: Mechanisms, evidence boundaries, and translational opportunities.Redox biology · 2026Review
- A novel model to study the impact of gender-affirming therapy on bone in young male mice.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2026Article
- [Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- Metabolomic analysis of gingival crevicular fluid for dental age and skeletal maturity assessment in growing individuals.European journal of orthodontics · 2026Article
- Transcriptomic Dissection ofInternational journal of molecular sciences · 2026Article
- Targeting the Ip6k2-Runx2 axis disrupts osteoblast-osteoclast coupling to treat osteoporosis.Nature communications · 2026Article
- Histone arginine demethylase JMJD7 promotes bone formation through regulating α-Ketoglutarate metabolism.Cell death and differentiation · 2026Article
- PHGDH Orchestrates Cell Cycle Progression to Drive Cardiomyocyte Proliferation and Myocardial Regeneration via TGF-β/Smad Signalling Pathway.Cell proliferation · 2026Article
- Changes in bone characteristics precede serum mineral deterioration in a mouse model of early stage chronic kidney disease.JBMR plus · 2026Article
- Macrophage Metabolic Reprogramming-Related Osteoimmunity in Osteoporosis.Calcified tissue international · 2026Review
- Nutrients and Metabolites as Signalling Molecules in Osteoclasts.Current osteoporosis reports · 2026Review
- PHGDH at the crossroads: metabolic plasticity, metastatic paradoxes, and therapeutic reconnaissance in cancer.Journal of biomedical science · 2026Review
- RANKL-convergent osteoimmune network framework in osteoporosis: integrating macrophage activation, T-cell imbalance, and cytokine crosstalk.Frontiers in immunology · 2026Review
- OptimizingPeerJ · 2026Article
- Uridine inhibits ROS-mediated osteoclast differentiation and alleviates osteoporosis via modulation of PI3K/Akt-FoxO signaling.Frontiers in immunology · 2026Article
- Regulation of osteoclastogenesis and bone resorption by fatty acid metabolism: mechanisms and therapeutic opportunities.Frontiers in endocrinology · 2026Review
- Mechanisms of osteoclast activation in inflammatory bone loss in rheumatoid arthritis.Nature reviews. Rheumatology · 2026Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Bone-resorbing osteoclasts are vital for postnatal bone health, as increased differentiation or activity results in skeletal pathologies such as osteoporosis. The metabolism of mature osteoclasts differs from their progenitor cells, but whether the observed metabolic changes are secondary to the altered cell state or actively drive the process of cell differentiation is unknown. Here, we show that transient activation of the serine synthesis pathway (SSP) is essential for osteoclastogenesis, as deletion of the rate-limiting enzyme phosphoglycerate dehydrogenase in osteoclast progenitors impairs their differentiation and results in increased bone mass. In addition, pharmacological phosphoglycerate dehydrogenase inhibition abrogated bone loss in a mouse model of postmenopausal osteoporosis by blocking bone resorption. Mechanistically, SSP-derived α-ketoglutarate is necessary for histone demethylases that remove repressive histone methylation marks at the nuclear factor of activated T cells, cytoplasmic 1 (Nfatc1) gene locus, thereby inducing NFATc1 expression and consequent osteoclast maturation. Taken together, this study reveals a metabolic-epigenetic coupling mechanism that directs osteoclast differentiation and suggests that the SSP can be therapeutically targeted to prevent osteoporotic bone loss.
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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.