ArticleThe Journal of biological chemistry2019
Mature osteoclast-derived apoptotic bodies promote osteogenic differentiation via RANKL-mediated reverse signaling.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 2 of them syntheses that pooled it.
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Who cites it
74 citing papers in PubMed, 2 syntheses or guidelines pooled it, 97 citations in OpenAlex.
- Mesenchymal stem cells-derived small extracellular vesicles and apoptotic extracellular vesicles for wound healing and skin regeneration: a systematic review and meta-analysis of preclinical studies.Journal of translational medicine · 2025Pooled it
- Serum RANKL levels in Chinese patients with ankylosing spondylitis: a meta-analysis.Journal of orthopaedic surgery and research · 2021Pooled it
- Vesicular Communication in the Bone-Muscle Unit: Physiological Functions, Aging, and Therapeutic Potential.Cells · 2026Review
- Apoptosis of Mdm2-deficient osteocytes enhances osteogenesis through TRPM8-enriched apoptotic vesicles.Bone research · 2026Article
- Apoptotic Bodies: Decoding Their Functional Messages in Physiology and Pathology.Cell biochemistry and function · 2026Review
- Apoptotic bodies in bone homeostasis and skeletal disease: biology and therapeutic implications.Apoptosis : an international journal on programmed cell death · 2026Review
- Apoptotic extracellular vesicles act as master regulators of the bone healing niche.Journal of nanobiotechnology · 2026Review
- Apoptotic extracellular vesicles: unveiling mechanisms, diverse functions, and biomedical implications.Apoptosis : an international journal on programmed cell death · 2026Review
- Large extracellular vesicles and blebbisomes in cancer: emerging and translational opportunities highlights.Cell communication and signaling : CCS · 2026Review
- The dual role of extracellular vesicles in vascular calcification: from molecular mechanisms to clinical translation.Frontiers in cardiovascular medicine · 2026Review
- Managing Rebound Bone Loss After Denosumab Discontinuation: Mechanisms, Risk Stratification, and Sequential Therapy.Drug design, development and therapy · 2026Review
- Exosomes in osteoporosis: regulatory mechanisms and clinical applications.Frontiers in physiology · 2026Review
- Bone homeostasis regulation by in vivo generation of osteoclast-derived apoptotic bodies using targeted self-assembly.Nature communications · 2025Article
- Mesenchymal stem cell-derived apoptotic vesicles: emerging cell-free strategy for periodontitis treatment.Journal of nanobiotechnology · 2025Review
- Rethinking the role of bisphosphonates after denosumab treatment in locally advanced or unresectable aneurysmal bone cysts: A meta-analysis.World journal of orthopedics · 2025Article
- Histological evaluation of osteogenesis using stem cells from human exfoliated deciduous teeth seeded in polymethylmethacrylate-hydroxyapatite scaffold.Journal of Taibah University Medical Sciences · 2025Article
- CCN Proteins as Matricellular Regulators of Bone in Aging and Disease.Current osteoporosis reports · 2025Review
- Recent Progress in Developing Extracellular Vesicles as Nanovehicles to Deliver Carbohydrate-Based Therapeutics and Vaccines.Vaccines · 2025Review
- Osteoclast-derived apoptotic bodies accelerate the pathological progression of osteoarthritis via disturbing subchondral bone remodeling.Journal of orthopaedic translation · 2025Article
- Bibliometric Analysis of Apoptotic Vesicles for Tissue Regeneration Research: Trends and Insights From 1991 to 2023.Stem cells international · 2025Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In bone remodeling, after a lifespan of ∼2 weeks, osteoclasts undergo apoptosis in each bone turnover cycle, resulting in generation of a large number of apoptotic bodies (ABs). However, the biological roles of osteoclast-derived ABs (OC-ABs) in bone remodeling have not been investigated and remain unknown. In this study, we stimulated bone marrow macrophages with receptor activator of NF-κB ligand (RANKL) to obtain both preosteoclasts and mature osteoclasts (mOCs). We then used alendronate to induce apoptosis in preosteoclasts and mOCs and generate the respective ABs and used flow cytometry and immunoblotting to characterize the sizes and immunogenic characteristics of the extracted ABs. We show that mOC-ABs are engulfed by preosteoblastic MC3T3-E1 cells and promote the viability of these cells. Among all osteoclast-derived extracellular vesicles, mOC-ABs had the highest osteogenic potency. We further observed that mOC-ABs had the highest vesicular receptor activator of NF-κB (RANK) levels among all types of osteoclast-derived extracellular vesicles. Of note, masking of vesicular RANK by soluble RANKL strongly abolished the osteogenic potency of osteoclast-derived ABs. Mechanistically, we found that mOC-ABs induce osteoblast differentiation by activatingPI3K/AKT/mechanistic target of rapamycin (mTOR)/ribosomal protein S6 kinase signaling. In conclusion, OC-ABs promote osteogenic differentiation by stimulating osteoblast differentiation via activation of RANKL reverse signaling. These findings provide important insights into the reversal phase between the bone resorption and formation stages during bone remodeling and identify an AB-dependent cellular signaling mechanism in osteoclast-osteoblast coupling.
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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.