Evidence map›Paper›PMID 42231949›Full record

ArticleiScience2026

Regulation of cAMP levels in osteocytes by mechano-sensitive focal adhesion kinase and phosphodiesterase 8A.

Garyfallia Papaioannou, Tadatoshi Sato, Caroline Houghton, Chuanqing Yan, Parthena E Kotsalidis, Katelyn E Strauss, Thomas Dean, Courtney M Mazur, Alissa J Nelson, Matthew P Stokes and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in iScience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. Osteocalcin and GPR158: linking bone and brain function.Frontiers in cell and developmental biology · 2025
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Garyfallia PapaioannouEndocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Tadatoshi SatoEndocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Caroline HoughtonEndocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Chuanqing YanChoate Rosemary Hall, Wallingford, CT, USA.
Parthena E KotsalidisEndocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Katelyn E StraussEndocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Thomas DeanEndocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Courtney M MazurEndocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Alissa J NelsonCell Signaling Technology, Inc., Danvers, MA, USA.
Matthew P StokesCell Signaling Technology, Inc., Danvers, MA, USA.
Thomas J GardellaEndocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Marc N WeinEndocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Osteocytes are the primary mechano-sensitive cell type in bone. Mechanical loading is sensed across the dendritic projections of osteocytes leading to transient reductions in focal adhesion kinase (FAK) activity. We performed tyrosine-focused phospho-proteomic profiling in osteocyte-like Ocy454 cells to identify FAK substrates. Gsα, parathyroid hormone receptor (PTH1R), and phosphodiesterase 8A (PDE8A), three proteins associated with cAMP signaling, were found as potential FAK targets. FAK pharmacologic inhibition or gene deletion increased basal and G-protein-coupled-receptor (GPCR) ligand-stimulated cAMP levels and downstream signaling events. PDE8A inhibition mimicked FAK inhibition at the levels of increased cAMP, protein kinase A (PKA) activity, and expression of cAMP-regulated target genes. Co-immunoprecipitation assays revealed an intracellular association between FAK and PDE8A. Thus, mechanically regulated FAK can modulate intracellular cAMP levels via effects on PDE8A. These data suggest a signal transduction mechanism that mediates crosstalk between mechanical and cAMP-linked hormonal signaling in osteocytes.

Indexed as

cell biologyendocrinologymolecular biology

Identifiers

PMID42231949
PMCPMC13224023

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.