Evidence map›Paper›PMID 18212126›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2008

Osteoblast expression of an engineered Gs-coupled receptor dramatically increases bone mass.

Edward C Hsiao, Benjamin M Boudignon, Wei C Chang, Margaret Bencsik, Jeffrey Peng, Trieu D Nguyen, Carlota Manalac, Bernard P Halloran, Bruce R Conklin, Robert A Nissenson

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed, 1 pooled it
3.6field-weighted citation impact, top 7% 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

69 citing papers in PubMed, 1 synthesis or guideline pooled it, 106 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Review
  6. Article
  7. Update on the medical management of fibrous dysplasia of the bone.Therapeutic advances in endocrinology and metabolism · 2025
    Review
  8. Article
  9. Increased Osteoblast GαJBMR plus · 2023
    Article
  10. Review
  11. Conditional Loss of Nmp4 in Mesenchymal Stem Progenitor Cells Enhances PTH-Induced Bone Formation.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2023
    Article
  12. Article
  13. Chemogenetics as a neuromodulatory approach to treating neuropsychiatric diseases and disorders.Molecular therapy : the journal of the American Society of Gene Therapy · 2022
    Review
  14. Article
  15. Kindlin-2 regulates skeletal homeostasis by modulating PTH1R in mice.Signal transduction and targeted therapy · 2020
    Article
  16. Article
  17. PET Imaging of Phosphodiesterase-4 Identifies Affected Dysplastic Bone in McCune-Albright Syndrome, a Genetic Mosaic Disorder.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2020
    Article
  18. Review
  19. Review
  20. Review

9 more citing papers are in PubMed but not listed here.

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

10 authors at 3 institutions in 1 country.

Edward C HsiaoGladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA. ehsiao@gladstone.ucsf.edu
Benjamin M Boudignon
Wei C Chang
Margaret Bencsik
Jeffrey Peng
Trieu D Nguyen
Carlota Manalac
Bernard P Halloran
Bruce R Conklin
Robert A Nissenson
University of California, San Francisco · USGladstone Institutes · USSan Francisco VA Medical Center · US

Funding

DIABETES, ENDOCRINOLOGY &METABOLISM TRAINING PROGRAMT32DK007418 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI EDWARD C HSIAO · 1986 to 2026
$14.3M
Tissue Engineering with a Modular RASSL ToolboxR01HL060664 · NHLBI · J. DAVID GLADSTONE INSTITUTES · PI CONKLIN, BRUCE R · 1998 to 2012
$7.0M
EXTRAMULAR RESEARCH FACILITIES CONSTRUCTIONC06RR018928 · NCRR · J. DAVID GLADSTONE INSTITUTES · PI MAHLEY, ROBERT W. · 2003 to 2003
$2.1M
G PROTEIN SIGNALING IN OSTEOBLASTSR01DK072071 · NIDDK · NORTHERN CALIFORNIA INSTITUTE/RES/EDU · PI NISSENSON, ROBERT · 2006 to 2009
$1.3M
G Protein Signaling in OsteoblastsR56DK072071 · NIDDK · NORTHERN CALIFORNIA INSTITUTE/RES/EDU · PI NISSENSON, ROBERT · 2010 to 2010
$222k
NCRR NIH HHS C06 RR018928NCRR NIH HHS RR18928-01NHLBI NIH HHS R01 HL060664NHLBI NIH HHS R01 HL60664-07NIDDK NIH HHS 2T32DK07418-26NIDDK NIH HHS DK072071NIDDK NIH HHS R01 DK072071NIDDK NIH HHS R56 DK072071NIDDK NIH HHS T32 DK007418
6 · The paper itself

Abstract

Osteoblasts are essential for maintaining bone mass, avoiding osteoporosis, and repairing injured bone. Activation of osteoblast G protein-coupled receptors (GPCRs), such as the parathyroid hormone receptor, can increase bone mass; however, the anabolic mechanisms are poorly understood. Here we use "Rs1," an engineered GPCR with constitutive G(s) signaling, to evaluate the temporal and skeletal effects of G(s) signaling in murine osteoblasts. In vivo, Rs1 expression induces a dramatic anabolic skeletal response, with midfemur girth increasing 1,200% and femur mass increasing 380% in 9-week-old mice. Bone volume, cellularity, areal bone mineral density, osteoblast gene markers, and serum bone turnover markers were also elevated. No such phenotype developed when Rs1 was expressed after the first 4 weeks of postnatal life, indicating an exquisite temporal sensitivity of osteoblasts to Rs1 expression. This pathway may represent an important determinant of bone mass and may open future avenues for enhancing bone repair and treating metabolic bone diseases.

Indexed as

Protein EngineeringAmino Acid SequenceAnimalsBone DensityCell LineFemaleGTP-Binding Protein alpha Subunits, GsHumansLigandsMaleMiceMice, TransgenicMolecular Sequence DataOsteoblastsReceptors, Serotonin, 5-HT4Serotonin 5-HT4 Receptor AgonistsGTP-Binding Protein alpha Subunits, GsLigandsReceptors, Serotonin, 5-HT4Serotonin 5-HT4 Receptor Agonists

Identifiers

PMID18212126
PMCPMC2234117
OpenAlexW2026225101

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.