Evidence map›Paper›PMID 23994943›Full record

ArticleJournal of the mechanical behavior of biomedical materials2013

Osteocyte differentiation is regulated by extracellular matrix stiffness and intercellular separation.

C A Mullen, M G Haugh, M B Schaffler, R J Majeska, L M McNamara

Open access · greenAbstract read
In one paragraph

Article in Journal of the mechanical behavior of biomedical materials, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed
3.9field-weighted citation impact, top 6% 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

53 citing papers in PubMed, 110 citations in OpenAlex.

  1. Article
  2. Review
  3. Bone Fragility: Time to Address the Matrix.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2026
    Article
  4. Article
  5. Bone Organoids: A Novel Tool for Modeling and Managing Skeletal Disorders in Diabetes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  6. Article
  7. Article
  8. Mechanosignaling in Osteoporosis: When Cells Feel the Force.International journal of molecular sciences · 2025
    Review
  9. Review
  10. Article
  11. Review
  12. Article
  13. Review
  14. Review
  15. Review
  16. Review
  17. Article
  18. Article
  19. Review
  20. 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

5 authors at 2 institutions in 2 countries.

C A MullenCentre for Biomechanics Research (BMEC), Mechanical and Biomedical Engineering, NUI Galway, Ireland; National Centre for Biomedical Engineering Science (NCBES), NUI Galway, Ireland.
M G Haugh
M B Schaffler
R J Majeska
L M McNamara
Ollscoil na Gaillimhe – University of Galway · IECity College of New York · US

Funding

Osteocyte Integrity and Bone RemodelingR01AR041210 · NIAMS · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI SCHAFFLER, MITCHELL B · 1997 to 2019
$5.8M
Structural, Molecular, and Functional Specialization in Osteocyte MechanosensingR01AR057139 · NIAMS · CITY COLLEGE OF NEW YORK · PI SCHAFFLER, MITCHELL B, SPRAY, DAVID C · 2010 to 2014
$2.5M
Diffuse microdamage in bone: Direct repair without remodelingR21AR060445 · NIAMS · CITY COLLEGE OF NEW YORK · PI SCHAFFLER, MITCHELL B · 2011 to 2012
$371k
MICRODAMAGE AND BONE REMODELING IN STRESS FRACTURER29AR041210 · NIAMS · HENRY FORD HEALTH SYSTEM · PI SCHAFFLER, MITCHELL B · 1992 to 1996
–
NIAMS NIH HHS AR041210NIAMS NIH HHS AR057139NIAMS NIH HHS R01 AR041210NIAMS NIH HHS R01 AR057139NIAMS NIH HHS R21 AR060445
6 · The paper itself

Abstract

Osteocytes are terminally differentiated bone cells, derived from osteoblasts, which are vital for the regulation of bone formation and resorption. ECM stiffness and cell seeding density have been shown to regulate osteoblast differentiation, but the precise cues that initiate osteoblast-osteocyte differentiation are not yet understood. In this study, we cultured MC3T3-E1 cells on (A) substrates of different chemical compositions and stiffnesses, as well as, (B) substrates of identical chemical composition but different stiffnesses. The effect of cell separation was investigated by seeding cells at different densities on each substrate. Cells were evaluated for morphology, alkaline phosphatase (ALP), matrix mineralisation, osteoblast specific genes (Type 1 collagen, Osteoblast specific factor (OSF-2)), and osteocyte specific proteins (dentin matrix protein 1 (DMP-1), sclerostin (Sost)). We found that osteocyte differentiation (confirmed by dendritic morphology, mineralisation, reduced ALP, Col type 1 and OSF-2 and increased DMP-1 and Sost expression) was significantly increased on soft collagen based substrates, at low seeding densities compared to cells on stiffer substrates or those plated at high seeding density. We propose that the physical nature of the ECM and the necessity for cells to establish a communication network contribute substantially to a concerted shift toward an osteocyte-like phenotype by osteoblasts in vitro.

Indexed as

Cell DifferentiationMechanical Phenomena3T3 CellsAlkaline PhosphataseAnimalsBiomechanical PhenomenaExtracellular MatrixGene Expression RegulationMiceMineralsOsteocytesAlkaline PhosphataseMineralsBoneCellular differentiationExtracellular mechanical environmentOsteoblastOsteocyte

Identifiers

PMID23994943
PMCPMC5776008
OpenAlexW2105240389

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.