ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2023
Endothelial Cell-Derived Lactate Triggers Bone Mesenchymal Stem Cell Histone Lactylation to Attenuate Osteoporosis.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers.
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Who cites it
112 citing papers in PubMed, 104 citations in OpenAlex.
- Lactylation and exercise: A molecular link to disease alleviation (Review).Molecular medicine reports · 2026Review
- Lactylation in gastric cancer: From mechanisms to clinical applications (Review).Molecular medicine reports · 2026Review
- Exercise-induced protein lactylation: From molecular mechanisms to precision health applications.iScience · 2026Review
- [Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2026Review
- The Role of Glucose Metabolic Reprogramming in Exercise-Attenuated Osteoporosis: a Narrative Review.Sports medicine - open · 2026Review
- Protein acylation and bone metabolism: bidirectional crosstalk linking metabolic reprogramming to skeletal homeostasis.Journal of molecular histology · 2026Review
- H3K18la in periodontal ligament fibroblasts regulates immune niches and alveolar bone remodeling under mechanical loads.International journal of oral science · 2026Article
- Glucose metabolism in osteoporosis: A potential therapeutic target (Review).International journal of molecular medicine · 2026Review
- Asprosin-driven metabolic-epigenetic rewiring attenuates mesenchymal stem cell senescence with therapeutic benefits for infarcted hearts.Journal of advanced research · 2026Article
- Puerarin‑Loaded pH‑Responsive ZIF‑90 Nanoparticles Ameliorate Osteoporosis via Enhancing H3K18 Lactylation and Suppressing Aberrant Osteoclast Activation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Glycolysis in bone remodeling: from energy supply to signaling regulation.Molecular biology reports · 2026Review
- Vascular-lymphatic dual circulation in bone health and disease: Mechanistic coupling and translational therapeutics.Journal of orthopaedic translation · 2026Review
- Mechanobiology of orofacial tissues: principles, mechanisms, and therapeutic applications.International journal of oral science · 2026Review
- Forkhead Box O1 Promotes Osteogenesis of Periodontal Ligament Stem Cells Via Glycolysis-Related Metabolic Reprogramming.International dental journal · 2026Article
- Lysine l-Lactylation: Bridging Metabolism, Chromatin and Disease.Cell proliferation · 2026Review
- Epigenetic Regulation of Bone Homeostasis in Osteoporosis: Mechanisms, Evidence Gaps, and Translational Prospects.Cell biochemistry and function · 2026Review
- Enhancing pulp regeneration through metabolic reprogramming of mature dental pulp stem cells mediated by GLUT1/HK2 mRNA delivery.International journal of oral science · 2026Article
- Protein lactylation in health and diseases: molecular mechanisms, biological significance, and clinical implications.Signal transduction and targeted therapy · 2026Review
- HK1-LDHA axis feedback regulation promotes histone lactylation of Wnt5a and mediates prenatal acetaminophen-induced susceptibility to osteoarthritis in male offspring.Experimental & molecular medicine · 2026Article
- The emerging role of lactate in skeletal homeostasis and disorders: Integrated mechanisms and translational opportunities.Journal of orthopaedic translation · 2026Review
52 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 6 institutions in 1 country.
Funding
Abstract
Blood vessels play a role in osteogenesis and osteoporosis; however, the role of vascular metabolism in these processes remains unclear. The present study finds that ovariectomized mice exhibit reduced blood vessel density in the bone and reduced expression of the endothelial glycolytic regulator pyruvate kinase M2 (PKM2). Endothelial cell (EC)-specific deletion of Pkm2 impairs osteogenesis and worsens osteoporosis in mice. This is attributed to the impaired ability of bone mesenchymal stem cells (BMSCs) to differentiate into osteoblasts. Mechanistically, EC-specific deletion of Pkm2 reduces serum lactate levels secreted by ECs, which affect histone lactylation in BMSCs. Using joint CUT&Tag and RNA sequencing analyses, collagen type I alpha 2 chain (COL1A2), cartilage oligomeric matrix protein (COMP), ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), and transcription factor 7 like 2 (TCF7L2) as osteogenic genes regulated by histone H3K18la lactylation are identified. PKM2 overexpression in ECs, lactate addition, and exercise restore the phenotype of endothelial PKM2-deficient mice. Furthermore, serum metabolomics indicate that patients with osteoporosis have relatively low lactate levels. Additionally, histone lactylation and related osteogenic genes of BMSCs are downregulated in patients with osteoporosis. In conclusion, glycolysis in ECs fuels BMSC differentiation into osteoblasts through histone lactylation, and exercise partially ameliorates osteoporosis by increasing serum lactate levels.
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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.