ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2017
A Novel, Direct NO Donor Regulates Osteoblast and Osteoclast Functions and Increases Bone Mass in Ovariectomized Mice.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.
- The Efficacy of Nitrates for Bone Health: A Systematic Review and Meta-Analysis of Observational and Randomized Controlled Studies.Frontiers in endocrinology · 2022Pooled it
- Nitric oxide modulates bone anabolism through regulation of osteoblast glycolysis and differentiation.The Journal of clinical investigation · 2021Trial
- Endothelial Nitric Oxide Synthase Restores Diabetic Dentin Regeneration via AKT/Endothelial Nitric Oxide Synthase Axis.International dental journal · 2026Article
- Spectrum and functions of ion channels and transporters in osteoclasts.Bone research · 2026Review
- Mitochondrial homeostasis restoring peptide-drug conjugates with ROS-responsive NO releasing ability for targeted therapy of myocardial infarction.Journal of nanobiotechnology · 2025Article
- Decoding different oxidative stress pathways in periodontitis: a comparative review of mechanisms of traditional tobacco smoke and electronic smoke aerosol.Archives of toxicology · 2025Review
- Biomineralized PEEK cages containing osteoinductive CaP bioceramics promote spinal fusion in goats.Bioactive materials · 2025Article
- Nitric oxide contributes to rapid sclerostin protein loss following mechanical load.Biochemical and biophysical research communications · 2024Article
- Tailoring of apoptotic bodies for diagnostic and therapeutic applications:advances, challenges, and prospects.Journal of translational medicine · 2024Review
- Naringenin modulates the NO‑cGMP‑PKG signaling pathway by binding to AKT to enhance osteogenic differentiation in hPDLSCs.International journal of molecular medicine · 2024Article
- A plasma membrane-associated form of the androgen receptor enhances nuclear androgen signaling in osteoblasts and prostate cancer cells.Science signaling · 2024Article
- A network pharmacological study to unveil the mechanisms of xianlinggubao capsule in the treatment of osteoarthritis and osteoporosis.Archives of medical science : AMS · 2024Article
- Dietary nitrate improves jaw bone remodelling in zoledronate-treated mice.Cell proliferation · 2023Article
- Identification of kukoamine a as an anti-osteoporosis drug target using network pharmacology and experiment verification.Molecular medicine (Cambridge, Mass.) · 2023Article
- Connection between Osteoarthritis and Nitric Oxide: From Pathophysiology to Therapeutic Target.Molecules (Basel, Switzerland) · 2023Review
- Protein Kinase G2 Is Essential for Skeletal Homeostasis and Adaptation to Mechanical Loading in Male but Not Female Mice.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2023Article
- Glycemic Control and Bone in Diabetes.Current osteoporosis reports · 2022Review
- Article
- Tadalafil and Steroid Hormones Interactions in Adipose, Bone and Prostate Tissues: Focus on Translational Perspectives.International journal of molecular sciences · 2022Review
- Control of Orthodontic Tooth Movement by Nitric Oxide Releasing Nanoparticles in Sprague-Dawley Rats.Frontiers in dental medicine · 2022Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
Most US Food and Drug Administration (FDA)-approved treatments for osteoporosis target osteoclastic bone resorption. Only PTH derivatives improve bone formation, but they have drawbacks, and novel bone-anabolic agents are needed. Nitrates, which generate NO, improved BMD in estrogen-deficient rats and may improve bone formation markers and BMD in postmenopausal women. However, nitrates are limited by induction of oxidative stress and development of tolerance, and may increase cardiovascular mortality after long-term use. Here we studied nitrosyl-cobinamide (NO-Cbi), a novel, direct NO-releasing agent, in a mouse model of estrogen deficiency-induced osteoporosis. In murine primary osteoblasts, NO-Cbi increased intracellular cGMP, Wnt/β-catenin signaling, proliferation, and osteoblastic gene expression, and protected cells from apoptosis. Correspondingly, in intact and ovariectomized (OVX) female C57Bl/6 mice, NO-Cbi increased serum cGMP concentrations, bone formation, and osteoblastic gene expression, and in OVX mice, it prevented osteocyte apoptosis. NO-Cbi reduced osteoclasts in intact mice and prevented the known increase in osteoclasts in OVX mice, partially through a reduction in the RANKL/osteoprotegerin gene expression ratio, which regulates osteoclast differentiation, and partially through direct inhibition of osteoclast differentiation, observed in vitro in the presence of excess RANKL. The positive NO effects in osteoblasts were mediated by cGMP/protein kinase G (PKG), but some of the osteoclast-inhibitory effects appeared to be cGMP-independent. NO-Cbi increased trabecular bone mass in both intact and OVX mice, consistent with its in vitro effects on osteoblasts and osteoclasts. NO-Cbi is a novel direct NO-releasing agent that, in contrast to nitrates, does not generate oxygen radicals, and combines anabolic and antiresorptive effects in bone, making it an excellent candidate for treating osteoporosis. © 2016 American Society for Bone and Mineral Research.
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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.