ArticleCell death & disease2014
Inhibition of phosphodiesterase 5 reduces bone mass by suppression of canonical Wnt signaling.
Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
- Assessing the therapeutic potential of PDE-5 inhibitors in adults: Insights from a multi-omics study.Physiological reports · 2026Article
- Phosphodiesterase inhibitors as emerging therapeutics for skeletal disorders: A comprehensive review of mechanisms and repurposing potential.Bone reports · 2026Review
- Emerging Mechanistic Insights and Therapeutic Strategies for Pulmonary Arterial Hypertension: A Focus on Right Ventricular Dysfunction and Novel Treatment Pathways.Biomedicines · 2025Review
- Vitamin C inactivates c-Jun N-terminal kinase to stabilize heart and neural crest derivatives expressed 1 (Hand1) in regulating placentation and maintenance of pregnancy.Cellular and molecular life sciences : CMLS · 2024Article
- Mass spectrometry-based phosphoproteomics in clinical applications.Trends in analytical chemistry : TRAC · 2023Article
- RhoA/Rock activation represents a new mechanism for inactivating Wnt/β-catenin signaling in the aging-associated bone loss.Cell regeneration (London, England) · 2021Article
- Inhibition of Phosphodiesterase 5 Promotes the Aromatase-Mediated Estrogen Biosynthesis in Osteoblastic Cells by Activation of cGMP/PKG/SHP2 Pathway.Frontiers in endocrinology · 2021Article
- The effect of two phosphodiesterase inhibitors on bone healing in mandibular fractures (animal study in rats).Journal of the Korean Association of Oral and Maxillofacial Surgeons · 2020Article
- 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
- Analysis of short-term treatment with the phosphodiesterase type 5 inhibitor tadalafil on long bone development in young rats.American journal of physiology. Endocrinology and metabolism · 2018Article
- The effect of PDE5 inhibitors on bone and oxidative damage in ovariectomy-induced osteoporosis.Experimental biology and medicine (Maywood, N.J.) · 2017Article
- Phosphoproteins in extracellular vesicles as candidate markers for breast cancer.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Assessment of the Role of NO-cGMP Pathway in Orthodontic Tooth Movement Using PDE5 Inhibitors: An Animal Study.Journal of dentistry (Tehran, Iran) · 2016Article
- Signaling Cascades Governing Cdc42-Mediated Chondrogenic Differentiation and Mensenchymal Condensation.Genetics · 2016Article
- Tadalafil modulates aromatase activity and androgen receptor expression in a human osteoblastic cell in vitro model.Journal of endocrinological investigation · 2016Article
- Article
- Sonic hedgehog through Gli2 and Gli3 is required for the proper development of placental labyrinth.Cell death & disease · 2015Article
- Pentoxifylline and electromagnetic field improved bone fracture healing in rats.Drug design, development and therapy · 2015Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inhibitors of phosphodiesterase 5 (PDE5) are widely used to treat erectile dysfunction and pulmonary hypertension in clinics. PDE5, cyclic guanosine monophosphate (cGMP), and protein kinase G (PKG) are important components of the non-canonical Wnt signaling. This study aimed to investigate the effect of PDE5 inhibition on canonical Wnt signaling and osteoblastogenesis, using both in vitro cell culture and in vivo animal models. In the in vitro experiments, PDE5 inhibition resulted in activation of cGMP-dependent protein kinase 2 and consequent inhibition of glycogen synthase kinase 3β phosphorylation, destabilization of cytosolic β-catenin and the ultimate suppression of canonical Wnt signaling and reduced osteoblastic differentiation in HEK293T and C3H10T1/2 cells. In animal experiments, systemic inhibition of PDE5 suppressed the activity of canonical Wnt signaling and osteoblastogenesis in bone marrow-derived stromal cells, resulting in the reduction of bone mass in wild-type adult C57B/6 mice, significantly attenuated secreted Frizzled-related protein-1 (SFRP1) deletion-induced activation of canonical Wnt signaling and excessive bone growth in adult SFRP1(-/-) mice. Together, these results uncover a hitherto uncharacterized role of PDE5/cGMP/PKG signaling in bone homeostasis and provide the evidence that long-term treatment with PDE5 inhibitors at a high dosage may potentially cause bone catabolism.
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