ArticleEndocrinology2014
Soluble guanylate cyclase as a novel treatment target for osteoporosis.
Article in Endocrinology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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.
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Who cites it
30 citing papers in PubMed, 45 citations in OpenAlex.
- Effects of soluble guanylate cyclase activator vericiguat on fracture healing in rats.Joint diseases and related surgery · 2026Article
- 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
- Naringenin modulates the NO‑cGMP‑PKG signaling pathway by binding to AKT to enhance osteogenic differentiation in hPDLSCs.International journal of molecular medicine · 2024Article
- Protein kinase G2 activation restores Wnt signaling and bone mass in glucocorticoid-induced osteoporosis in mice.JCI insight · 2024Article
- A plasma membrane-associated form of the androgen receptor enhances nuclear androgen signaling in osteoblasts and prostate cancer cells.Science signaling · 2024Article
- 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
- 8-Nitro-cGMP suppresses mineralization by mouse osteoblasts.Journal of clinical biochemistry and nutrition · 2022Article
- Guanylyl Cyclase-B Dependent Bone Formation in Mice is Associated with Youth, Increased Osteoblasts, and Decreased Osteoclasts.Calcified tissue international · 2022Article
- Targeting Sirt1, AMPK, Nrf2, CK2, and Soluble Guanylate Cyclase with Nutraceuticals: A Practical Strategy for Preserving Bone Mass.International journal of molecular sciences · 2022Review
- The Role of Nitric Oxide in Stem Cell Biology.Antioxidants (Basel, Switzerland) · 2022Review
- Vericiguat Modulates Osteoclast Differentiation and Bone Resorption via a Balance between VASP and NF-Mediators of inflammation · 2022Article
- Management of Osteoporosis in Men: A Narrative Review.International journal of molecular sciences · 2021Review
- Cyclic GMP-Dependent Regulation of Vascular Tone and Blood Pressure Involves Cysteine-Rich LIM-Only Protein 4 (CRP4).International journal of molecular sciences · 2021Article
- Role of nitric oxide in orthodontic tooth movement (Review).International journal of molecular medicine · 2021Review
- The NO-cGMP-PKG pathway in skeletal remodeling.Annals of the New York Academy of Sciences · 2021Review
- Inflammation in the Human Periodontium Induces Downregulation of the αInternational journal of molecular sciences · 2021Article
- Pharmic Activation of PKG2 Alleviates Diabetes-Induced Osteoblast Dysfunction by Suppressing PLCOxidative medicine and cellular longevity · 2021Article
- Diabetoporosis: Role of nitric oxide.EXCLI journal · 2021Review
- Repurposing erectile dysfunction drugs tadalafil and vardenafil to increase bone mass.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Production of 8-nitro-cGMP in osteocytic cells and its upregulation by parathyroid hormone and prostaglandin EIn vitro cellular & developmental biology. Animal · 2019Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Osteoporosis is a major health problem leading to fractures that cause substantial morbidity and mortality. Current osteoporosis therapies have significant drawbacks, creating a need for novel bone-anabolic agents. We previously showed that the nitric oxide/cyclic GMP (cGMP)/protein kinase G pathway mediates some of the anabolic effects of estrogens and mechanical stimulation in osteoblasts and osteocytes, leading us to hypothesize that cGMP-elevating agents may have bone-protective effects. We tested cinaciguat, a prototype of a novel class of soluble guanylate cyclase activators, in a mouse model of estrogen deficiency-induced osteoporosis. Compared with sham-operated mice, ovariectomized mice had lower serum cGMP concentrations, which were largely restored to normal by treatment with cinaciguat or low-dose 17β-estradiol. Microcomputed tomography of tibiae showed that cinaciguat significantly improved trabecular bone microarchitecture in ovariectomized animals, with effect sizes similar to those obtained with estrogen replacement therapy. Cinaciguat reversed ovariectomy-induced osteocyte apoptosis as efficiently as estradiol and enhanced bone formation parameters in vivo, consistent with in vitro effects on osteoblast proliferation, differentiation, and survival. Compared with 17β-estradiol, which completely reversed the ovariectomy-induced increase in osteoclast number, cinaciguat had little effect on osteoclasts. Direct guanylate cyclase stimulators have been extremely well tolerated in clinical trials of cardiovascular diseases, and our findings provide proof-of-concept for this new class of drugs as a novel, anabolic treatment strategy for postmenopausal osteoporosis, confirming an important role of nitric oxide/cGMP/protein kinase G signaling in bone.
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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.