Osteoclast-derived exosomal miR-214-3p inhibits osteoblastic bone formation
Open accessAbstract
Emerging evidence indicates that osteoclasts direct osteoblastic bone formation. MicroRNAs (miRNAs) have a crucial role in regulating osteoclast and osteoblast function. However, whether miRNAs mediate osteoclast-directed osteoblastic bone formation is mostly unknown. Here, we show that increased osteoclastic miR-214-3p associates with both elevated serum exosomal miR-214-3p and reduced bone formation in elderly women with fractures and in ovariectomized (OVX) mice. Osteoclast-specific miR-214-3p knock-in mice have elevated serum exosomal miR-214-3p and reduced bone formation that is rescued by osteoclast-targeted antagomir-214-3p treatment. We further demonstrate that osteoclast-derived exosomal miR-214-3p is transferred to osteoblasts to inhibit osteoblast activity in vitro and reduce bone formation in vivo. Moreover, osteoclast-targeted miR-214-3p inhibition promotes bone formation in ageing OVX mice. Collectively, our results suggest that osteoclast-derived exosomal miR-214-3p transfers to osteoblasts to inhibit bone formation. Inhibition of miR-214-3p in osteoclasts may be a strategy for treating skeletal disorders involving a reduction in bone formation.
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During remodeling, osteoclast-derived apoptotic bodies containing miR-214-3p are delivered to osteoblasts and inhibit osteoblast differentiation and subsequent bone formation.
“During remodeling, osteoclast-derived apoptotic bodies containing miR-214-3p are delivered to osteoblasts and serve as intercellular messengers that inhibit osteoblast differentiation and subsequent bone formation.249”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [249]
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- Authors
- Li, D., Liu, J., Guo, B., Liang, C., Dang, L., Lu, C., He, X., Cheung, H. Y.-S., Xu, L., Lu, C., He, B., Liu, B., Shaikh, A. B., Li, F., Wang, L., Yang, Z., Au, D. W.-T., Peng, S., Zhang, Z., Zhang, B.-T., Pan, X., Qian, A., Shang, P., Xiao, L., Jiang, B., Wong, C. K.-C., Xu, J., Bian, Z., Liang, Z., Guo, D.-A., Zhu, H., Tan, W., Lu, A., & Zhang, G.
- Affiliations
- Hong Kong Baptist University (HK)
- City University of Hong Kong (HK)
- Chinese University of Hong Kong (HK)
- Chinese Academy of Sciences (CN)
- The University of Western Australia (AU)
- Corresponding author
- Zhang, Ge
- ORCID
- Li, Defang
- Liu, Jin
- Guo, Baosheng
- Liang, Chao
- Dang, Lei
- Lu, Cheng
- He, Xiaojuan
- Xu, Liang
- Lu, Changwei
- Liu, Biao
- Wang, Luyao
- Yang, Zhijun
- Au, Doris Wai-Ting
- Peng, Songlin
- Zhang, Zongkang
- Zhang, Bao-Ting
- Pan, Xiaohua
- Qian, Airong
- Shang, Peng
- Xiao, Lianbo
- Jiang, Baohong
- Wong, Chris Kong-Chu
- Xu, Jiake
- Bian, Zhaoxiang
- Liang, Zicai
- Guo, De-an
- Zhu, Hailong
- Tan, Weihong
- Zhang, Ge
- Venue
- Nature Communications
- Published
- 2016-03-07
- Volume
- 7
- Issue
- 1
- Pages
- 10872-10872
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC4786676
- OpenAlex
- W2299414460
- Cited by
- 588
- References
- 48
- Citations by year
- 2026: 29 · 2025: 40 · 2024: 61 · 2023: 68 · 2022: 97 · 2021: 89 · 2020: 60 · 2019: 65 · 2018: 39 · 2017: 27 · 2016: 10
- FWCI
- 24.42
- Type
- journal article
- Language
- en
- Update notices
- correction (2025-06-19)
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- UWA Profiles and Research Repository (UWA) (publishedVersion, cc-by)
- PubMed (publishedVersion)
- CityU Scholars (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Croucher Foundation (Gnt#CAS14BU/CAS14201, CAS14201, CAS14BU/CAS14201)
- Hong Kong Baptist University (FRG2/14-15/010, SDF13-1209-P01, FRG2/13-14/006, RC-IRMS/12-13/02, RC-IRMS/13-14/02)
- Chinese University of Hong Kong
- China Academy of Chinese Medical Sciences (Z0293, Z0252)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Keywords
- miR-214-3p, osteoclasts, exosomes, osteoblasts, bone formation, microRNA transfer, ovariectomy, postmenopausal osteoporosis, fracture, aging, bone loss
- MeSH terms
- Aged, Aged, 80 and over, Animals, Bone and Bones, Bone Development, Cells, Cultured, Female, Humans, Male, Mice, Inbred C57BL, Middle Aged, Osteoclasts, Down-Regulation, Case-Control Studies, Mice, Knockout, MicroRNAs, Fractures, Bone, Mice, Exosomes
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