Trial reportThe Journal of clinical investigation2021
Nitric oxide modulates bone anabolism through regulation of osteoblast glycolysis and differentiation.
Trial report in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
47 citing papers in PubMed, 78 citations in OpenAlex.
- Amino Acid Metabolism in Health and Disease.MedComm · 2026Review
- The Role of Endothelial Dysfunction in Fracture Healing: Mechanisms and Potential Effects on Skeletal Repair.International journal of molecular sciences · 2026Review
- The Effects of Arginine, Guanidinoacetic Acid and Citrulline Supplementation to Reduced Protein Diets for Aged Laying Hens.Animals : an open access journal from MDPI · 2026Article
- Txnip regulates glycolysis and tricarboxylic acid cycle balance to maintain bone homeostasis.Journal of orthopaedic translation · 2026Article
- Histone arginine demethylase JMJD7 promotes bone formation through regulating α-Ketoglutarate metabolism.Cell death and differentiation · 2026Article
- Bone Marrow Mesenchymal Stromal Cell Osteogenesis is driven by Paracrine signals from Regulatory T Cell.Stem cell reviews and reports · 2026Article
- Metabolic Rewiring and Post-Translational Modifications: Unlocking the Mechanisms of Bone Turnover in Osteoporosis.Aging and disease · 2025Review
- Arginine metabolism in myeloid cells in health and disease.Seminars in immunopathology · 2025Review
- Cracking the code: Understanding ESWT's role in bone fracture healing.Journal of orthopaedic translation · 2025Review
- Gender-Specific effects of L-arginine supplementation on bone mineral density and trabecular bone volume in Sprague-Dawley rats; stereological study.BMC complementary medicine and therapies · 2024Article
- Integrative in-silico and in-vitro analysis of taurine and vitamin B12 in modulating PPARγ and Wnt signaling in hyperhomocysteinemia-induced osteoporosis.Biology direct · 2024Article
- Itaconate is a metabolic regulator of bone formation in homeostasis and arthritis.Annals of the rheumatic diseases · 2024Article
- Metabolic reprogramming in skeletal cell differentiation.Bone research · 2024Review
- A photothermal responsive system accelerating nitric oxide release to enhance bone repair by promoting osteogenesis and angiogenesis.Materials today. Bio · 2024Article
- Nitric oxide contributes to rapid sclerostin protein loss following mechanical load.Biochemical and biophysical research communications · 2024Article
- Skeletal Muscle, Skin, and Bone as Three Major Nitrate Reservoirs in Mammals: Chemiluminescence andNutrients · 2024Article
- The IFITM5 mutation in osteogenesis imperfecta type V is associated with an ERK/SOX9-dependent osteoprogenitor differentiation defect.The Journal of clinical investigation · 2024Article
- Fueling recovery: The importance of energy coupling between angiogenesis and osteogenesis during fracture healing.Bone reports · 2024Review
- SIRT1 maintains bone homeostasis by regulating osteoblast glycolysis through GOT1.Cellular and molecular life sciences : CMLS · 2024Article
- mRNA therapy corrects defective glutathione metabolism and restores ureagenesis in preclinical argininosuccinic aciduria.Science translational medicine · 2024Article
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Previous studies have shown that nitric oxide (NO) supplements may prevent bone loss and fractures in preclinical models of estrogen deficiency. However, the mechanisms by which NO modulates bone anabolism remain largely unclear. Argininosuccinate lyase (ASL) is the only mammalian enzyme capable of synthesizing arginine, the sole precursor for nitric oxide synthase-dependent (NOS-dependent) NO synthesis. Moreover, ASL is also required for channeling extracellular arginine to NOS for NO production. ASL deficiency (ASLD) is thus a model to study cell-autonomous, NOS-dependent NO deficiency. Here, we report that loss of ASL led to decreased NO production and impairment of osteoblast differentiation. Mechanistically, the bone phenotype was at least in part driven by the loss of NO-mediated activation of the glycolysis pathway in osteoblasts that led to decreased osteoblast differentiation and function. Heterozygous deletion of caveolin 1, a negative regulator of NO synthesis, restored NO production, osteoblast differentiation, glycolysis, and bone mass in a hypomorphic mouse model of ASLD. The translational significance of these preclinical studies was further reiterated by studies conducted in induced pluripotent stem cells from an individual with ASLD. Taken together, our findings suggest that ASLD is a unique genetic model for studying NO-dependent osteoblast function and that the NO/glycolysis pathway may be a new target to modulate bone anabolism.
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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.