Cited by 169Connexins and lens biologyBone Metabolism and DiseasesBone health and osteoporosis research

Low peak bone mass and attenuated anabolic response to parathyroid hormone in mice with an osteoblast-specific deletion of connexin43

Open access
Chung, Dong Jin, Castro, Charlles H. M., Watkins, Marcus, Stains, Joseph P., Chung, Min Young, Szejnfeld, Vera Lucia, Willecke, Klaus, Theis, Martin +1 more·2006·Journal of Cell Science

Abstract

Connexin43 (Cx43) is involved in bone development, but its role in adult bone homeostasis remains unknown. To overcome the postnatal lethality of Cx43 null mutation, we generated mice with selective osteoblast ablation of Cx43, obtained using a Cx43fl allele and a 2.3-kb fragment of the α1(I) collagen promoter to drive Cre in osteoblasts (ColCre). Conditionally osteoblast-deleted ColCre;Cx43–/fl mice show no malformations at birth, but develop low peak bone mass and remain osteopenic with age, exhibiting reduced bone formation and defective osteoblast function. By both radiodensitometry and histology, bone mineral content increased rapidly and progressively in adult Cx43+/fl mice after subcutaneous injection of parathyroid hormone (PTH), an effect significantly attenuated in ColCre;Cx43–/fl mice, with Cx43–/fl exhibiting an intermediate response. Attenuation of PTH anabolic action was associated with failure to increase mineral apposition rate in response to PTH in ColCre;Cx43–/fl, despite an increased osteoblast number, suggesting a functional defect in Cx43-deficient bone-forming cells. In conclusion, lack of Cx43 in osteoblasts leads to suboptimal acquisition of peak bone mass, and hinders the bone anabolic effect of PTH. Cx43 represents a potential target for modulation of bone anabolism.

Integrity signals

Registry

Crossref · 10.1242/jcs.03162

Cites

58 of 58 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

  • FFSS induces the disruption of the FAK-integrin complex, thereby inhibiting HDAC4/5, a negative regulator of SOST expression in osteocytes modulated by PTH treatment.

    “Recently, Sato et al.20,44 showed that FFSS induces the disruption of the FAK-integrin complex, thereby inhibiting histone deacetylase 4/5 (HDAC4/5), a negative regulator of SOST expression in osteocytes45 modulated by parathyroid hormone (PTH) treatment.46”
  • 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.”

Cites

Flagged first, then by citations

1 of the 59 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Authors
Chung, D. J., Castro, C. H. M., Watkins, M., Stains, J. P., Chung, M. Y., Szejnfeld, V. L., Willecke, K., Theis, M., & Civitelli, R.
Affiliations
  • Chonnam National University (KR)
  • Division of Bone and Mineral Diseases, Washington University School of Medicine, 660 S. Euclid Avenue, St Louis, MO 63110, USA
  • Washington University in St. Louis (US)
  • Universidade Federal de São Paulo-Escola Paulista de Medicina, São Paulo, Brasil
  • University of Bonn (DE)
Corresponding author
Civitelli, Roberto
Venue
Journal of Cell Science
Published
2006-10-15
Volume
119
Issue
20
Pages
4187-4198
ISSN
  • 0021-9533 (ISSN-L)
  • 1477-9137
OpenAlex
W2092039312
Cited by
169
References
59
Citations by year
2026: 2 · 2025: 2 · 2024: 5 · 2023: 7 · 2022: 5 · 2021: 4 · 2020: 9 · 2019: 7 · 2018: 5 · 2017: 10 · 2016: 15 · 2015: 8 · 2014: 10 · 2013: 15 · 2012: 13
FWCI
3.26
Type
journal article
Language
en
Open access
Licence
other-oa
Locations
  • Journal of Cell Science (publishedVersion)
  • PubMed (publishedVersion)
  • Americanae (AECID Library) (submittedVersion, other-oa)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
Funders
  • National Institute of Diabetes and Digestive and Kidney Diseases (P30DK056341)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR041255)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
  • Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
Keywords
connexin 43, osteoblasts, parathyroid hormone, peak bone mass, bone formation, osteopenia, bone homeostasis, conditional knockout mice, Cre-loxP system
MeSH terms
Animals, Bone and Bones, Mice, Transgenic, Osteoblasts, Osteogenesis, Parathyroid Hormone, Phenotype, Blotting, Western, Bone Density, Gene Deletion, Gap Junctions, Connexin 43, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, Cell Proliferation, Mice

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