ArticleThe Journal of biological chemistry2014
High bone mass in mice lacking Cx37 because of defective osteoclast differentiation.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 62 citations in OpenAlex.
- Article
- Presenilin L166P Mutation, a Model of Familial Alzheimer's Disease, Leads to Early Onset Bone Loss.Comprehensive Physiology · 2026Article
- Skeletal abnormalities caused by a Connexin43Bone research · 2025Article
- Family-based whole-exome sequencing implicates a variant in lysyl oxidase like 4 in atypical femur fractures.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2024Article
- Independent contribution of gonads and sex chromosomes to sex differences in bone mass and strength in the four-core genotypes mouse model.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2024Article
- Connexin43 in Musculoskeletal System: New Targets for Development and Disease Progression.Aging and disease · 2022Article
- miR21 deletion in osteocytes has direct and indirect effects on skeletal muscle in a sex-dimorphic manner in mice.Biology of sex differences · 2022Article
- Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) R47H Variant Causes Distinct Age- and Sex-Dependent Musculoskeletal Alterations in Mice.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Article
- Targeting Endothelial Connexin37 Reduces Angiogenesis and Decreases Tumor Growth.International journal of molecular sciences · 2022Article
- Non-bone metastatic cancers promote osteocyte-induced bone destruction.Cancer letters · 2021Article
- Cellular and molecular actors of myeloid cell fusion: podosomes and tunneling nanotubes call the tune.Cellular and molecular life sciences : CMLS · 2021Review
- Antagonistic Functions of Connexin 43 during the Development of Primary or Secondary Bone Tumors.Biomolecules · 2020Review
- Osteocytic miR21 deficiency improves bone strength independent of sex despite having sex divergent effects on osteocyte viability and bone turnover.The FEBS journal · 2020Article
- The Role of Connexin Channels in the Response of Mechanical Loading and Unloading of Bone.International journal of molecular sciences · 2020Review
- Gap Junctions in the Bone Marrow Lympho-Hematopoietic Stem Cell Niche, Leukemia Progression, and Chemoresistance.International journal of molecular sciences · 2020Review
- Article
- Molecular signaling in bone cells: Regulation of cell differentiation and survival.Advances in protein chemistry and structural biology · 2019Review
- Bone physiology as inspiration for tissue regenerative therapies.Biomaterials · 2018Review
- Article
- Cx43 overexpression in osteocytes prevents osteocyte apoptosis and preserves cortical bone quality in aging mice.JBMR plus · 2018Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Connexin (Cx) proteins are essential for cell differentiation, function, and survival in all tissues with Cx43 being the most studied in bone. We now report that Cx37, another member of the connexin family of proteins, is expressed in osteoclasts, osteoblasts, and osteocytes. Mice with global deletion of Cx37 (Cx37(-/-)) exhibit higher bone mineral density, cancellous bone volume, and mechanical strength compared with wild type littermates. Osteoclast number and surface are significantly lower in bone of Cx37(-/-) mice. In contrast, osteoblast number and surface and bone formation rate in bones from Cx37(-/-) mice are unchanged. Moreover, markers of osteoblast activity ex vivo and in vivo are similar to those of Cx37(+/+) littermates. sRANKL/M-CSF treatment of nonadherent Cx37(-/-) bone marrow cells rendered a 5-fold lower level of osteoclast differentiation compared with Cx37(+/+) cell cultures. Further, Cx37(-/-) osteoclasts are smaller and have fewer nuclei per cell. Expression of RANK, TRAP, cathepsin K, calcitonin receptor, matrix metalloproteinase 9, NFATc1, DC-STAMP, ATP6v0d1, and CD44, markers of osteoclast number, fusion, or activity, is lower in Cx37(-/-) osteoclasts compared with controls. In addition, nonadherent bone marrow cells from Cx37(-/-) mice exhibit higher levels of markers for osteoclast precursors, suggesting altered osteoclast differentiation. The reduction of osteoclast differentiation is associated with activation of Notch signaling. We conclude that Cx37 is required for osteoclast differentiation and fusion, and its absence leads to arrested osteoclast maturation and high bone mass in mice. These findings demonstrate a previously unrecognized role of Cx37 in bone homeostasis that is not compensated for by Cx43 in vivo.
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Registered trials
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.