Evidence map›Paper›PMID 25331517›Full record

ArticleJournal of orthopaedic research : official publication of the Orthopaedic Research Society2015

Systemic injection of CK2.3, a novel peptide acting downstream of bone morphogenetic protein receptor BMPRIa, leads to increased trabecular bone mass.

Hemanth Akkiraju, Jeremy Bonor, Kristine Olli, Chris Bowen, Beth Bragdon, Harold Coombs, Leah Rae Donahue, Randall Duncan, Anja Nohe

Abstract read
In one paragraph

Article in Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
–field-weighted citation impact
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

21 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Review
  5. The Role of BMP Signaling in Osteoclast Regulation.Journal of developmental biology · 2021
    Review
  6. Aberrant BMP2 Signaling in Patients Diagnosed with Osteoporosis.International journal of molecular sciences · 2020
    Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Bone Morphogenetic Protein-Based Therapeutic Approaches.Cold Spring Harbor perspectives in biology · 2018
    Review
  15. Article
  16. CK2.1, a novel peptide, induces articular cartilage formation in vivo.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2017
    Article
  17. Review
  18. Article
  19. Article
  20. An Improved Immunostaining and Imaging Methodology to Determine Cell and Protein Distributions within the Bone Environment.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2016
    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

9 authors.

Hemanth AkkirajuDepartment of Biological Sciences, University of Delaware, Newark, Delaware.
Jeremy Bonor
Kristine Olli
Chris Bowen
Beth Bragdon
Harold Coombs
Leah Rae Donahue
Randall Duncan
Anja Nohe

Funding

Predictive Modeling & Optimal Control Framework for Model-Based Epidemic Response in DelawareP20GM103446 · NIGMS · UNIVERSITY OF DELAWARE · PI Anjana Narayan Bhat · 2012 to 2026
$67.2M
Mechanism of a mimetic peptide CK2.3 on bone formationR01AR064243 · NIAMS · UNIVERSITY OF DELAWARE · PI NOHE, ANJA G · 2013 to 2018
$1.6M
NIAMS NIH HHS R01 AR064243NIGMS NIH HHS P20 GM103446
6 · The paper itself

Abstract

Bone Morphogenetic Protein 2 (BMP2) regulates bone integrity by driving both osteogenesis and osteoclastogenesis. However, BMP2 as a therapeutic has significant drawbacks. We have designed a novel peptide CK2.3 that blocks the interaction of Casein Kinase 2 (CK2) with Bone Morphogenetic Protein Receptor type Ia (BMPRIa), thereby activating BMP signaling pathways in the absence of ligand. Here, we show that CK2.3 induced mineralization in primary osteoblast cultures isolated from calvaria and bone marrow stromal cells (BMSCs) of 8 week old mice. Further, systemic tail vein injections of CK2.3 in 8 week old mice resulted in increased bone mineral density (BMD) and mineral apposition rate (MAR). In situ immunohistochemistry of the femur found that CK2.3 injection induced phosphorylation of extracellular signal-related kinase (ERK), but not Smad in osteocytes and osteoblasts, suggesting that CK2.3 signaling occurred through Smad independent pathway. Finally mice injected with CK2.3 exhibited decreased osteoclast differentiation and osteoclast activity. These data indicate that the novel mimetic peptide CK2.3 activated BMPRIa downstream signaling to enhance bone formation without the increase in osteoclast activity that accompanies BMP 2 stimulation.

Indexed as

AnimalsAnimals, NewbornBiomarkersBone DensityBone Morphogenetic Protein Receptors, Type ICasein Kinase IICells, CulturedDrug Evaluation, PreclinicalExtracellular Signal-Regulated MAP KinasesFemaleMesenchymal Stem CellsMice, Inbred C57BLOsteoclastsOsteogenesisPeptidesSkullBiomarkersBmpr1a protein, mouseBone Morphogenetic Protein Receptors, Type ICasein Kinase IIExtracellular Signal-Regulated MAP KinasesPeptidesSmad Proteinsbone mineral densitybone morphogenetic proteincasein kinase 2mimetic peptideosteoporosis

Identifiers

PMID25331517
PMCPMC4304894

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Registered trials

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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.