Evidence map›Paper›PMID 22189870›Full record

ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2012

Examination of nuclear receptor expression in osteoblasts reveals Rorβ as an important regulator of osteogenesis.

Matthew M Roforth, Gang Liu, Sundeep Khosla, David G Monroe

Open access · bronzeAbstract read
In one paragraph

Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 1 pooled it
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

26 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.

  1. Consequences of Aging on Bone.Aging and disease · 2023
    Pooled it
  2. Article
  3. Review
  4. Article
  5. Article
  6. RORβ Deficiency Inhibits Endochondral Ossification in Mice by Mediating the HIF-1α/VEGFA Signaling Pathway.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Prostaglandin EStem cell reviews and reports · 2021
    Article
  13. Article
  14. Article
  15. miR-219a-5p Regulates Rorβ During Osteoblast Differentiation and in Age-related Bone Loss.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2019
    Article
  16. Identification of potent RORβ modulators: Scaffold variation.Bioorganic & medicinal chemistry letters · 2018
    Article
  17. Identification of an aminothiazole series of RORβ modulators.Bioorganic & medicinal chemistry letters · 2018
    Article
  18. Osteoprotection Through the Deletion of the Transcription Factor Rorβ in Mice.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2018
    Article
  19. Review
  20. The multi-faceted role of retinoid X receptor in bone remodeling.Cellular and molecular life sciences : CMLS · 2017
    Review
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

4 authors at 1 institution in 1 country.

Matthew M RoforthEndocrine Research Unit, College of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Gang Liu
Sundeep Khosla
David G Monroe
Mayo Clinic · US

Funding

SEX STEROIDS, GROWTH FACTORS, &BONE CELL FUNCTIONP01AG004875 · NIA · MAYO CLINIC ROCHESTER · PI KHOSLA, SUNDEEP · 1985 to 2019
$30.8M
NIA NIH HHS P01 AG004875NIA NIH HHS P01-AG004875
6 · The paper itself

Abstract

A complex network of transcription factors contributes to the establishment and maintenance of the osteoblastic phenotype. Although relatively few transcription factors, such as Runx2 and osterix, are essential to the process of osteoblastic differentiation, others serve the purpose of fine-tuning in response to various environmental and hormonal cues. The nuclear receptor (NR) superfamily of transcription factors are involved in numerous aspects of bone biology. In this study, we characterized the expression pattern of the entire NR superfamily in differentiating primary murine calvarial cells in order to identify novel NR regulatory patterns. Dynamic patterns of NR expression were observed throughout the differentiation process. Interestingly, retinoic acid receptor-related orphan receptor β (Rorβ) expression was markedly suppressed at later stages of differentiation. To gain further insight into the function of NRs in bone biology, the NR superfamily was also profiled in mouse bone marrow precursor cells isolated from either young (6-month) or aging, osteoporotic (18-22-month) mice. Of interest, Rorβ was potently overexpressed in the aged cohort. Collectively, these data provided evidence that Rorβ expression is inversely correlated with osteogenic potential, suggesting Rorβ may be an important and unexplored regulator of osteogenesis. To validate this hypothesis, a cell model stably expressing Rorβ in mouse osteoblastic MC3T3-E1 cells was produced (MC3T3-Rorβ). These cells displayed markedly suppressed bone nodule formation as well as reduced osteocalcin and osterix gene expression. Because these genes are Runx2 targets, we reasoned that Rorβ may interfere with Runx2 activity. Consistent with this, transient transfection analysis demonstrated that Rorβ inhibited Runx2-dependent activation of a Runx2-reporter construct. In summary, our data provide a comprehensive profile of NR expression during osteoblast differentiation and identify Rorβ as a novel regulator of osteogenesis and potentially of age-related bone loss through antagonism of Runx2 activity.

Indexed as

OsteogenesisAnimalsBiomarkersCalcification, PhysiologicCell DifferentiationCell LineCell LineageCore Binding Factor Alpha 1 SubunitGene Expression RegulationHumansMiceMice, Inbred C57BLNuclear Receptor Subfamily 1, Group F, Member 2OsteoblastsOsteocytesSkullBiomarkersCore Binding Factor Alpha 1 SubunitNuclear Receptor Subfamily 1, Group F, Member 2Rorb protein, mouseRunx2 protein, mouse

Identifiers

PMID22189870
PMCPMC3667501
OpenAlexW2006153980

What OpenQuestion holds

Textmetadata
LicenceTDM
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.