ArticleScientific reports2019
Endothelial Progenitor Cells inhibit jaw osteonecrosis in a rat model: A major adverse effect of bisphosphonate therapy.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- In Vitro Cytotoxicity of Antiresorptive and Antiangiogenic Compounds on Oral Tissues Contributing to MRONJ: Systematic Review.Biomolecules · 2023Pooled it
- Mechanism-Oriented Biomaterial Strategies for Bone Regeneration in BRONJ: From Pathological Barriers to Evidence-Matched Repair.Biomolecules · 2026Review
- Cytotoxicity and antifungal effects of combined dexamethasone and miconazole on human oral keratinocytes, gingival fibroblasts, and Candida albicans.Odontology · 2026Article
- Novel standardized method for inducing medication-related osteonecrosis of the jaw in rats and precise quantitative assessment of pathological outcomes.Odontology · 2025Article
- Mechanisms Underlying Medication-Related Osteonecrosis of the Jaw.Oral diseases · 2025Review
- Rodents as an animal model for studying tooth extraction-related medication-related osteonecrosis of the jaw: assessment of outcomes.Archives of oral biology · 2024Review
- Inflammation Can Be a High-Risk Factor for Mucosal Nonunion of MRONJ by Regulating SIRT1 Signaling When Treated with an Oncologic Dose of Zoledronate.Drug design, development and therapy · 2024Article
- Therapeutic application of regeneration-associated cells: a novel source of regenerative medicine.Stem cell research & therapy · 2023Review
- Article
- Anti-angiogenic drug aggravates the degree of anti-resorptive drug-based medication-related osteonecrosis of the jaw by impairing the proliferation and migration function of gingival fibroblasts.BMC oral health · 2023Article
- Exosomes Derived from Adipose Tissue-Derived Mesenchymal Stromal Cells Prevent Medication-Related Osteonecrosis of the Jaw through IL-1RA.International journal of molecular sciences · 2023Article
- Endothelial Progenitor Cells Promote Osteosarcoma Progression and Invasiveness via AKT/PI3K Signaling.Cancers · 2023Article
- Could Local Application of Hypoxia Inducible Factor 1-α Enhancer Deferoxamine Be Promising for Preventing of Medication-Related Osteonecrosis of the Jaw?Biomedicines · 2023Article
- Oral fibroblasts rescue osteogenic differentiation of mesenchymal stem cells after exposure to Zoledronic acid in a paracrine effect.Frontiers in pharmacology · 2023Article
- Significance of medication discontinuation on bisphosphonate-related jaw osteonecrosis in a rat model.Scientific reports · 2022Article
- Establishment and assessment of rodent models of medication-related osteonecrosis of the jaw (MRONJ).International journal of oral science · 2022Review
- How zoledronic acid improves osteoporosis by acting on osteoclasts.Frontiers in pharmacology · 2022Review
- Review
- Pilot investigation on the dose-dependent impact of irradiation on primary human alveolar osteoblasts in vitro.Scientific reports · 2021Article
- Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse effect of antiresorptive and antiangiogenic therapies. MRONJ is identified by chronic wounds in the oral mucosa associated with exposed necrotic bone. We hypothesized that zoledronic acid (ZOL) impairs keratinocyte and fibroblast function and reduces soft tissue vascularization; therefore, treating MRONJ with proangiogenic cells may benefit MRONJ patients. The effect of ZOL and dexamethasone (DEX) on gingival fibroblasts and keratinocytes was investigated. In-vitro, ZOL inhibited fibroblast and keratinocyte proliferation, delaying scratch healing. In-vivo, exposed bone was detected at tooth extraction sites, mainly in ZOL(+)/DEX(+) rats; and was associated with significantly decreased soft tissue vascularization, serum-VEGF, and tissue-VEGF. Local injection of early and late endothelial progenitor cells (EPCs) healed 13 of 14 MRONJ lesions compared with 2/7 lesions in the mesenchymal stem cells, and 2/6, in culture-medium group. The EPCs reduced necrotic bone area, increased serum and tissue VEGF levels. EPCs engraftment was minimal, suggesting their paracrine role in MRONJ healing. The EPC-conditioned medium improved scratch healing of keratinocytes and fibroblasts via VEGF pathway and elevated mRNA of VEGFA and collagen1A1. In conclusion, a novel MRONJ treatment with EPCs, increased vascularization and improved epithelial and fibroblast functions as well as cured the lesion.
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