CoChat
Sign Up
Cited by 148Bone Metabolism and DiseasesConnexins and lens biologyBone health and osteoporosis research

Enhanced Osteoclastic Resorption and Responsiveness to Mechanical Load in Gap Junction Deficient Bone

Open access
Zhang, Yue, Paul, Emmanuel M., Sathyendra, Vikram, Davison, Andrew, Sharkey, Neil, Bronson, Sarah, Srinivasan, Sundar, Gross, Ted S. +1 more·2011·PLoS ONE
DOI 10.1371/journal.pone.0023516PMC PMC3163577
Open this paper in CoChat — free accountOpen PDF

Abstract

Emerging evidence suggests that connexin mediated gap junctional intercellular communication contributes to many aspects of bone biology including bone development, maintenance of bone homeostasis and responsiveness of bone cells to diverse extracellular signals. Deletion of connexin 43, the predominant gap junction protein in bone, is embryonic lethal making it challenging to examine the role of connexin 43 in bone in vivo. However, transgenic murine models in which only osteocytes and osteoblasts are deficient in connexin 43, and which are fully viable, have recently been developed. Unfortunately, the bone phenotype of different connexin 43 deficient models has been variable. To address this issue, we used an osteocalcin driven Cre-lox system to create osteoblast and osteocyte specific connexin 43 deficient mice. These mice displayed bone loss as a result of increased bone resorption and osteoclastogenesis. The mechanism underlying this increased osteoclastogenesis included increases in the osteocytic, but not osteoblastic, RANKL/OPG ratio. Previous in vitro studies suggest that connexin 43 deficient bone cells are less responsive to biomechanical signals. Interestingly, and in contrast to in vitro studies, we found that connexin 43 deficient mice displayed an enhanced anabolic response to mechanical load. Our results suggest that transient inhibition of connexin 43 expression and gap junctional intercellular communication may prove a potentially powerful means of enhancing the anabolic response of bone to mechanical loading.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1371/journal.pone.0023516

Cites

63 of 63 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Conditional knockout of Cx43 in osteoblasts and osteocytes in mice led to various degrees of osteopenia depending on the differentiation state in which the deletion was induced, suggesting that functional Cx43 in osteoblasts and osteocytes is essential for normal bone mass acquisition and maintenance.

    “Conditional knockout of Cx43 in osteoblasts and osteocytes in mice led to various degrees of osteopenia depending on the differentiation state in which the deletion was induced,20,21 suggesting that functional Cx43 in osteoblasts and osteocytes is essential for normal bone mass acquisition and maintenance.”

    From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [21]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. [54]Saunders MM You J Trosko JE Yamasaki H Li Z 2001 Gap junctions and fluid flow response in MC3T3-E1 cells. Am J Physiol Cell Physiol 281 C1917 1925 11698250

Cited by

Sorted by citations

Related

Authors
Zhang, Y., Paul, E. M., Sathyendra, V., Davison, A., Sharkey, N., Bronson, S., Srinivasan, S., Gross, T. S., & Donahue, H. J.
Affiliations
  • Pennsylvania State University (US)
  • University of Washington (US)
Corresponding author
Donahue, Henry J.
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2011-08-29
Volume
6
Issue
8
Pages
e23516
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0023516
PMC
PMC3163577
OpenAlex
W2022309828
Cited by
148
References
63
Citations by year
2026: 1 · 2025: 2 · 2024: 6 · 2023: 7 · 2022: 11 · 2021: 8 · 2020: 19 · 2019: 11 · 2018: 4 · 2017: 8 · 2016: 7 · 2015: 12 · 2014: 15 · 2013: 20 · 2012: 16
FWCI
6.75
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • University of Pennsylvania
  • Pennsylvania State University
  • National Institutes of Health
  • Penn State College of Medicine
  • National Institute on Aging (R01AG013087)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (R03AR057546)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
  • Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
Keywords
connexin 43, gap junctional intercellular communication, osteoclastogenesis, bone resorption, osteocytes, osteoblasts, RANKL/OPG ratio, mechanical loading, bone loss
MeSH terms
Animals, Biomechanical Phenomena, Bone and Bones, Bone Resorption, Cell Communication, Cell Line, Humans, Male, Osteoclasts, Osteocytes, Osteogenesis, RNA, Messenger, Bone Density, Gene Deletion, Gap Junctions, Connexin 43, Mice, Osteoprotegerin, RANK Ligand, Mechanical Phenomena

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review