ArticleScience signaling2010
Cyclic GMP and protein kinase G control a Src-containing mechanosome in osteoblasts.
Article in Science signaling, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 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.
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Who cites it
56 citing papers in PubMed, 94 citations in OpenAlex.
- Protein kinase G and focal adhesion kinase converge on Src/Akt/β-catenin signaling module in osteoblast mechanotransduction.The Journal of biological chemistry · 2012Trial
- SHP2-mediated ROS activation induces chondrocyte paraptosis in osteoarthritis and is attenuated by low-intensity pulsed ultrasound.Journal of orthopaedic translation · 2025Article
- Thyroid Hormone Action by Genomic and Nongenomic Molecular Mechanisms.Methods in molecular biology (Clifton, N.J.) · 2025Article
- 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
- Energizing Healing with Electromagnetic Field Therapy in Musculoskeletal Disorders.Journal of orthopaedics and sports medicine · 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
- Control of Orthodontic Tooth Movement by Nitric Oxide Releasing Nanoparticles in Sprague-Dawley Rats.Frontiers in dental medicine · 2022Article
- Protein tyrosine phosphatases in skeletal development and diseases.Bone research · 2022Review
- Vericiguat Modulates Osteoclast Differentiation and Bone Resorption via a Balance between VASP and NF-Mediators of inflammation · 2022Article
- Role of nitric oxide in orthodontic tooth movement (Review).International journal of molecular medicine · 2021Review
- Skeletal Functions of Voltage Sensitive Calcium Channels.Current osteoporosis reports · 2021Review
- The NO-cGMP-PKG pathway in skeletal remodeling.Annals of the New York Academy of Sciences · 2021Review
- Nutraceutical Aid for Allergies - Strategies for Down-Regulating Mast Cell Degranulation.Journal of asthma and allergy · 2021Review
- Pharmic Activation of PKG2 Alleviates Diabetes-Induced Osteoblast Dysfunction by Suppressing PLCOxidative medicine and cellular longevity · 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
- Protein kinase G1 regulates bone regeneration and rescues diabetic fracture healing.JCI insight · 2020Article
- Phosphodiesterase 10A Is a Mediator of Osteogenic Differentiation and Mechanotransduction in Bone Marrow-Derived Mesenchymal Stromal Cells.Stem cells international · 2020Article
- Is NO the Answer? The Nitric Oxide Pathway Can Support Bone Morphogenetic Protein 2 Mediated Signaling.Cells · 2019Article
- Dose-dependent roles of aspirin and other non-steroidal anti-inflammatory drugs in abnormal bone remodeling and skeletal regeneration.Cell & bioscience · 2019Review
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Mechanical stimulation is crucial for bone growth and remodeling, and fluid shear stress promotes anabolic responses in osteoblasts through multiple second messengers, including nitric oxide (NO). NO triggers production of cyclic guanosine 3',5'-monophosphate (cGMP), which in turn activates protein kinase G (PKG). We found that the NO-cGMP-PKG signaling pathway activates Src in mechanically stimulated osteoblasts to initiate a proliferative response. PKGII was necessary for Src activation, a process that also required the interaction of Src with β₃ integrins and dephosphorylation of Src by a complex containing the phosphatases SHP-1 (Src homology 2 domain-containing tyrosine phosphatase 1) and SHP-2. PKGII directly phosphorylated and stimulated SHP-1 activity, and fluid shear stress triggered the recruitment of PKGII, Src, SHP-1, and SHP-2 to a mechanosome containing β₃ integrins. PKGII-null mice showed defective Src and ERK (extracellular signal-regulated kinase) signaling in osteoblasts and decreased ERK-dependent gene expression in bone. Our findings reveal a convergence of NO-cGMP-PKG and integrin signaling and establish a previously unknown mechanism of Src activation. These results support the use of PKG-activating drugs to mimic the anabolic effects of mechanical stimulation of bone in the treatment of osteoporosis.
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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.