ArticleThe Journal of biological chemistry2009
Type II cGMP-dependent protein kinase mediates osteoblast mechanotransduction.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 101 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
- Phosphodiesterase inhibitors as emerging therapeutics for skeletal disorders: A comprehensive review of mechanisms and repurposing potential.Bone reports · 2026Review
- Vericiguat Attenuates Vascular Calcification by Cyclic Guanosine Monophosphate-Protein Kinase G Pathway Mediated Suppression of Matrix Metalloproteinase 10.Journal of the American Heart Association · 2026Article
- Sirt1: An Increasingly Interesting Molecule with a Potential Role in Bone Metabolism and Osteoporosis.Biomolecules · 2024Review
- A plasma membrane-associated form of the androgen receptor enhances nuclear androgen signaling in osteoblasts and prostate cancer cells.Science signaling · 2024Article
- Bone repair and key signalling pathways for cell-based bone regenerative therapy: A review.Journal of Taibah University Medical Sciences · 2023Review
- Shear Stress Drives the Cleavage Activation of Protease-Activated Receptor 2 by PRSS3/Mesotrypsin to Promote Invasion and Metastasis of Circulating Lung Cancer Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- 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
- Article
- Control of Orthodontic Tooth Movement by Nitric Oxide Releasing Nanoparticles in Sprague-Dawley Rats.Frontiers in dental medicine · 2022Article
- Kinase activity profiling identifies putative downstream targets of cGMP/PKG signaling in inherited retinal neurodegeneration.Cell death discovery · 2022Article
- Hypertension meets osteoarthritis - revisiting the vascular aetiology hypothesis.Nature reviews. Rheumatology · 2021Review
- Role of nitric oxide in orthodontic tooth movement (Review).International journal of molecular medicine · 2021Review
- Protein kinase G1 regulates bone regeneration and rescues diabetic fracture healing.JCI insight · 2020Article
- Review
- Phosphodiesterase 10A Is a Mediator of Osteogenic Differentiation and Mechanotransduction in Bone Marrow-Derived Mesenchymal Stromal Cells.Stem cells international · 2020Article
- Mechanotransduction in osteogenesis.Bone & joint research · 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
- cGMP-dependent protein kinase-2 regulates bone mass and prevents diabetic bone loss.The Journal of endocrinology · 2018Article
- Nitric oxide and cyclic GMP functions in bone.Nitric oxide : biology and chemistry · 2018Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Continuous bone remodeling in response to mechanical loading is critical for skeletal integrity, and interstitial fluid flow is an important stimulus for osteoblast/osteocyte growth and differentiation. However, the biochemical signals mediating osteoblast anabolic responses to mechanical stimulation are incompletely understood. In primary human osteoblasts and murine MC3T3-E1 cells, we found that fluid shear stress induced rapid expression of c-fos, fra-1, fra-2, and fosB/DeltafosB mRNAs; these genes encode transcriptional regulators that maintain skeletal integrity. Fluid shear stress increased osteoblast nitric oxide (NO) synthesis, leading to activation of cGMP-dependent protein kinase (PKG). Pharmacological inhibition of the NO/cGMP/PKG signaling pathway blocked shear-induced expression of all four fos family genes. Induction of these genes required signaling through MEK/Erk, and Erk activation was NO/cGMP/PKG-dependent. Treating cells with a membrane-permeable cGMP analog partly mimicked the effects of fluid shear stress on Erk activity and fos family gene expression. In cells transfected with small interfering RNAs (siRNA) specific for membrane-bound PKG II, shear- and cGMP-induced Erk activation and fos family gene expression was nearly abolished and could be restored by transducing cells with a virus encoding an siRNA-resistant form of PKG II; in contrast, siRNA-mediated repression of the more abundant cytosolic PKG I isoform was without effect. Thus, we report a novel function for PKG II in osteoblast mechanotransduction, and we propose a model whereby NO/cGMP/PKG II-mediated Erk activation and induction of c-fos, fra-1, fra-2, and fosB/DeltafosB play a key role in the osteoblast anabolic response to mechanical stimulation.
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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.