ArticleJCI insight2023
CCL3 in the bone marrow microenvironment causes bone loss and bone marrow adiposity in aged mice.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Rejuvenation of Bone Marrow Mesenchymal Stem Cells: Mechanisms and Their Application in Senile Osteoporosis Treatment.Biomolecules · 2025Pooled it
- Cellular senescence and the SASP in skeletal ageing: convergent mechanisms of progressive bone loss in osteoporosis.Biogerontology · 2026Review
- CSF1R+ macrophage and osteoclast depletion impairs neural crest proliferation and craniofacial morphogenesis.Development (Cambridge, England) · 2026Article
- Gestational Protein Restriction Promotes Osteoporotic Phenotype During Aging.Calcified tissue international · 2026Article
- The osteoporotic niche as a metabolic sanctuary for breast cancer dormancy and reactivation: A mechanistic perspective.iScience · 2026Review
- Expansion of bone marrow adipocytes in obese mice leads to PD-L1-driven bone marrow immunosuppression and osteoclastogenesis.Bone research · 2026Article
- Aging-related metabolic dysregulation in osteoporosis: mechanisms and therapeutic strategies.Frontiers in aging · 2026Review
- Bidirectional regulation factor of bone marrow mesenchymal stromal cells differentiation: a focus on bone-fat balance in osteoporosis.Stem cell research & therapy · 2025Review
- Piezo1 activation suppresses bone marrow adipogenesis to prevent osteoporosis by inhibiting a mechanoinflammatory autocrine loop.Signal transduction and targeted therapy · 2025Article
- A traditional herbal decoction regulates skeletal muscle satellite cell osteogenesis and myogenesis for repairing osteosarcopenic fractures via β-catenin.Stem cell research & therapy · 2025Article
- Gene Expression Changes as Biomarkers of Immunosenescence in Bulgarian Individuals of Active Age.Biomedicines · 2025Article
- Targeting NAMPT-OPA1 for treatment of senile osteoporosis.Aging cell · 2025Article
- Oversecretion of CCL3 by Irradiation-Induced Senescent Osteocytes Mediates Bone Homeostasis Imbalance.Cells · 2025Article
- Function and Regulation of Bone Marrow Adipose Tissue in Health and Disease: State of the Field and Clinical Considerations.Comprehensive Physiology · 2024Review
- Heterogeneous osteoimmune profiles via single-cell transcriptomics in osteoporotic patients who fail bisphosphonate treatment.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Decoding the immune landscape following hip fracture in elderly patients: unveiling temporal dynamics through single-cell RNA sequencing.Immunity & ageing : I & A · 2023Article
- Leveraging mice with diverse microbial exposures for advances in osteoimmunology.Frontiers in endocrinology · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The central physiological role of the bone marrow renders bone marrow stromal cells (BMSCs) particularly sensitive to aging. With bone aging, BMSCs acquire a differentiation potential bias in favor of adipogenesis over osteogenesis, and the underlying molecular mechanisms remain unclear. Herein, we investigated the factors underlying age-related changes in the bone marrow and their roles in BMSCs' differentiation. Antibody array revealed that CC chemokine ligand 3 (CCL3) accumulation occurred in the serum of naturally aged mice along with bone aging phenotypes, including bone loss, bone marrow adiposity, and imbalanced BMSC differentiation. In vivo Ccl3 deletion could rescue these phenotypes in aged mice. CCL3 improved the adipogenic differentiation potential of BMSCs, with a positive feedback loop between CCL3 and C/EBPα. CCL3 activated C/EBPα expression via STAT3, while C/EBPα activated CCL3 expression through direct promoter binding, facilitated by DNA hypomethylation. Moreover, CCL3 inhibited BMSCs' osteogenic differentiation potential by blocking β-catenin activity mediated by ERK-activated Dickkopf-related protein 1 upregulation. Blocking CCL3 in vivo via neutralizing antibodies ameliorated trabecular bone loss and bone marrow adiposity in aged mice. This study provides insights regarding age-related bone loss and bone marrow adiposity pathogenesis and lays a foundation for the identification of new targets for senile osteoporosis treatment.
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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.