Evidence map›Paper›PMID 32315291›Full record

ArticleJCI insight2020

Protein kinase G1 regulates bone regeneration and rescues diabetic fracture healing.

Nadine Schall, Julian J Garcia, Hema Kalyanaraman, Shyamsundar Pal China, Jenna J Lee, Robert L Sah, Alexander Pfeifer, Renate B Pilz

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
0.8field-weighted citation impact, top 29% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 24 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. m6A: a novel strategy for osteoporosis treatment.Frontiers in cell and developmental biology · 2025
    Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Thyrotropin, Hyperthyroidism, and Bone Mass.The Journal of clinical endocrinology and metabolism · 2021
    Review
  15. Article
  16. Article
  17. The NO-cGMP-PKG pathway in skeletal remodeling.Annals of the New York Academy of Sciences · 2021
    Review
  18. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 2 countries.

Nadine SchallDepartment of Medicine, University of California, San Diego, La Jolla, California, USA.
Julian J GarciaDepartment of Medicine, University of California, San Diego, La Jolla, California, USA.
Hema KalyanaramanDepartment of Medicine, University of California, San Diego, La Jolla, California, USA.
Shyamsundar Pal ChinaDepartment of Medicine, University of California, San Diego, La Jolla, California, USA.
Jenna J LeeDepartment of Bioengineering, University of California, San Diego, La Jolla, California, USA.
Robert L SahDepartment of Bioengineering, University of California, San Diego, La Jolla, California, USA.
Alexander PfeiferInstitute for Pharmacology and Toxicology, University of Bonn, Bonn, Germany.
Renate B PilzDepartment of Medicine, University of California, San Diego, La Jolla, California, USA.
University of California San Diego · USUniversity of Bonn · DE

Funding

U of Calif, San Diego Neuroscience Microscopy ImagingP30NS047101 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G, ZHENG, BINHAI · 2003 to 2022
$9.0M
Targeting defective NO/cGMP signaling as novel therapy for diabetic osteoporosisR01AR068601 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI PILZ, RENATE B · 2016 to 2020
$1.8M
NIAMS NIH HHS R01 AR068601NINDS NIH HHS P30 NS047101
6 · The paper itself

Abstract

Bone fractures are a major cause of morbidity and mortality, particularly in patients with diabetes, who have a high incidence of fractures and exhibit poor fracture healing. Coordinated expression of osteoblast-derived vascular endothelial growth factor (VEGF) and bone morphogenic proteins (BMPs) is essential for fracture repair. The NO/cGMP/protein kinase G (PKG) signaling pathway mediates osteoblast responses to estrogens and mechanical stimulation, but the pathway's role in bone regeneration is unknown. Here, we used a mouse cortical-defect model to simulate bone fractures and studied osteoblast-specific PKG1-knockout and diabetic mice. The knockout mice had normal bone microarchitecture but after injury exhibited poor bone regeneration, with decreased osteoblasts, collagen deposition, and microvessels in the bone defect area. Primary osteoblasts and tibiae from the knockout mice expressed low amounts of Vegfa and Bmp2/4 mRNAs, and PKG1 was required for cGMP-stimulated expression of these genes. Diabetic mice also demonstrated low Vegfa and Bmp2/4 expression in bone and impaired bone regeneration after injury; notably, the cGMP-elevating agent cinaciguat restored Vegfa and BMP2/4 expression and full bone healing. We conclude that PKG1 is a key orchestrator of VEGF and BMP signaling during bone regeneration and propose pharmacological PKG activation as a novel therapeutic approach to enhance fracture healing.

Indexed as

Bone RegenerationDiabetes Mellitus, ExperimentalFracture HealingOsteoblastsAnimalsBone Morphogenetic Protein 2Bone Morphogenetic Protein 4Cyclic GMP-Dependent Protein KinasesCyclic GMP-Dependent Protein Kinase Type IFractures, BoneMaleMiceMice, Inbred C57BLMice, KnockoutVascular Endothelial Growth Factor ABmp2 protein, mouseBmp4 protein, mouseBone Morphogenetic Protein 2Bone Morphogenetic Protein 4Cyclic GMP-Dependent Protein KinasesCyclic GMP-Dependent Protein Kinase Type IPrkg1 protein, mouseVascular Endothelial Growth Factor Avascular endothelial growth factor A, mouseBone BiologyBone diseaseDiabetesSignal transduction

Identifiers

PMID32315291
PMCPMC7253025
OpenAlexW3017261050

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.