RANKL signaling in bone marrow mesenchymal stem cells negatively regulates osteoblastic bone formation
Open accessAbstract
RANKL signaling is essential for osteoclastogenesis. Its role in osteoblastic differentiation and bone formation is unknown. Here we demonstrate that RANK is expressed at an early stage of bone marrow mesenchymal stem cells (BMSCs) during osteogenic differentiation in both mice and human and decreased rapidly. RANKL signaling inhibits osteogenesis by promoting β-catenin degradation and inhibiting its synthesis. In contrast, RANKL signaling has no significant effects on adipogenesis of BMSCs. Interestingly, conditional knockout of rank in BMSCs with Prx1-Cre mice leads to a higher bone mass and increased trabecular bone formation independent of osteoclasts. In addition, rankflox/flox: Prx1-Cre mice show resistance to ovariectomy-(OVX) induced bone loss. Thus, our results reveal that RANKL signaling regulates both osteoclasts and osteoblasts by inhibition of osteogenic differentiation of BMSCs and promotion of osteoclastogenesis.
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It is more likely that DMAB blocks RANKL expressed on bone marrow mesenchymal stem cells, through which it negatively regulates osteogenic differentiation.
“It is more likely that DMAB blocks RANKL expressed on bone marrow mesenchymal stem cells (BMSCs),243 through which it negatively regulates osteogenic differentiation.244”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [244]
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References 26 · Cited by 154
- Authors
- Chen, X., Zhi, X., Wang, J., & Su, J.
- Affiliations
- Second Military Medical University (CN)
- Fudan University (CN)
- Corresponding author
- Su, Jiacan
- Venue
- Bone Research
- Published
- 2018-11-27
- Volume
- 6
- Issue
- 1
- Pages
- 34-34
- ISSN
- 2095-4700 (ISSN-L)
- 2095-6231
- PMC
- PMC6255918
- OpenAlex
- W2902142810
- Cited by
- 154
- References
- 26
- Citations by year
- 2026: 13 · 2025: 16 · 2024: 12 · 2023: 24 · 2022: 26 · 2021: 17 · 2020: 28 · 2019: 17 · 2018: 1
- FWCI
- 5.60
- Type
- journal article
- Language
- en
- Update notices
- correction (2022-08-15)
- Open access
- gold
- doi.org
- Locations
- Bone Research (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)
- Funders
- National Natural Science Foundation of China (91749204, 81771491, 81501052)
- Topics
- 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
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- RANKL signaling, RANK, bone marrow mesenchymal stem cells, osteogenic differentiation, osteoblasts, bone formation, β-catenin degradation, osteoclastogenesis, trabecular bone, ovariectomy-induced bone loss, adipogenesis
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