ReviewAnnals of the New York Academy of Sciences2021
The NO-cGMP-PKG pathway in skeletal remodeling.
Review in Annals of the New York Academy of Sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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
29 citing papers in PubMed, 62 citations in OpenAlex.
- Harnessing gasotransmitters for orthopaedic infection therapy: Mechanisms and advanced delivery platforms.Bioactive materials · 2027Review
- Phosphodiesterase inhibitors as emerging therapeutics for skeletal disorders: A comprehensive review of mechanisms and repurposing potential.Bone reports · 2026Review
- Pathway-Level Reorganization of Genetic Signals Associated with Low Bone Mineral Density Across the Menopausal Transition.International journal of molecular sciences · 2026Article
- Advanced multifunctional thermo- and electro-stimulative hydrogels for bone regeneration.Materials today. Bio · 2026Review
- Multiorgan and gut microbial alterations in ovariectomized mice: a multiomics analysis.Frontiers in immunology · 2026Article
- The nitrate-nitrite-nitric oxide pathway of neuroinflammation and cognitive impairment in ischemic stroke.Frontiers in immunology · 2026Review
- Effects of defatted black soldier fly larvae meal on growth, nutrient digestibility, hepatopancreas biochemistry, intestinal microbiota, and phosphorus discharge of giant freshwater prawn (Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2025Article
- Repeated-Dose Toxicity of Lauric Acid and Its Preventive Effect Against Tracheal Hyper-Responsiveness in Wistar Rats with PossiblePharmaceuticals (Basel, Switzerland) · 2025Article
- Cyclic di-AMP alleviates periodontitis by activating PI3K/Akt/Nrf2 pathways.Frontiers in cellular and infection microbiology · 2025Article
- Exosomes derived from miR-26a-5p-modified adipose mesenchymal stem cells improve wound healing by targetingFrontiers in bioengineering and biotechnology · 2025Article
- Impact of Medications for Stable Angina Pectoris on Osteoporosis: A Review of Current Evidence.Journal of multidisciplinary healthcare · 2025Review
- A monoallelic variant in CCN2 causes an autosomal dominant spondyloepimetaphyseal dysplasia with low bone mass.Bone research · 2024Article
- A photothermal responsive system accelerating nitric oxide release to enhance bone repair by promoting osteogenesis and angiogenesis.Materials today. Bio · 2024Article
- Skeletal Muscle, Skin, and Bone as Three Major Nitrate Reservoirs in Mammals: Chemiluminescence andNutrients · 2024Article
- Naringenin modulates the NO‑cGMP‑PKG signaling pathway by binding to AKT to enhance osteogenic differentiation in hPDLSCs.International journal of molecular medicine · 2024Article
- Identification and experimental validation of programmed cell death- and mitochondria-associated biomarkers in osteoporosis and immune microenvironment.Frontiers in genetics · 2024Article
- Isopsoralen Improves Glucocorticoid-induced Osteoporosis by Regulating Purine Metabolism and Promoting cGMP/PKG Pathway-mediated Osteoblast Differentiation.Current drug metabolism · 2024Article
- The effects of prophylactic tadalafil use on VEGF expression in the rabbit model of steroid-induced femoral head avascular necrosis.Acta orthopaedica et traumatologica turcica · 2023Article
- The 10th International Conference on cGMP 2022: recent trends in cGMP research and development-meeting report.Naunyn-Schmiedeberg's archives of pharmacology · 2023Review
- Dietary nitrate improves jaw bone remodelling in zoledronate-treated mice.Cell proliferation · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The nitric oxide (NO)-cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) pathway plays a critical role in skeletal homeostasis. Preclinical data using NO and its donors and genetically modified mice demonstrated that NO was required in bone remodeling and partly mediated the anabolic effects of mechanical stimuli and estrogen. However, the off-target effects and tachyphylaxis of NO limit its long-term use, and previous clinical trials using organic nitrates for osteoporosis have been disappointing. Among the other components in the downstream pathway, targeting cGMP-specific phosphodiesterase to promote the NO-cGMP-PKG signal is a viable option. There are growing in vitro and in vivo data that, among many other PDE families, PDE5A is highly expressed in skeletal tissue, and inhibiting PDE5A using currently available PDE5A inhibitors might increase the osteoanabolic signal and protect the skeleton. These preclinical data open the possibility of repurposing PDE5A inhibitors for treating osteoporosis. Further research is needed to address the primary target bone cell of PDE5A inhibition, the contribution of direct and indirect effects of PDE5A inhibition, and the pathophysiological changes in skeletal PDE5A expression in aging and hypogonadal animal models.
Indexed as
Identifiers
What Socratic holds
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 Socratic graph.