ArticleClinical oral investigations2015
BRONJ-related jaw bone is associated with increased Dlx-5 and suppressed osteopontin-implication in the site-specific alteration of angiogenesis and bone turnover by bisphosphonates.
Article in Clinical oral investigations, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Medication-Related Osteonecrosis of the Jaw: A Systematic Review and a Bioinformatic Analysis.International journal of molecular sciences · 2023Pooled it
- Comparison of Bacterial Adhesion on Two Different Suture Materials After Tooth Extraction in Women Receiving Antiresorptive Therapy: An Exploratory Clinical Study with Prospective Data Collection.Journal of clinical medicine · 2026Article
- Uncovering the unique characteristics of the mandible to improve clinical approaches to mandibular regeneration.Frontiers in physiology · 2023Review
- Bevacizumab and sunitinib mediate osteogenic and pro-inflammatory molecular changes in primary human alveolar osteoblasts in vitro.Odontology · 2022Article
- The Special Developmental Biology of Craniofacial Tissues Enables the Understanding of Oral and Maxillofacial Physiology and Diseases.International journal of molecular sciences · 2021Review
- Zoledronate Causes a Systemic Shift of Macrophage Polarization towards M1 In Vivo.International journal of molecular sciences · 2021Article
- Small Extracellular Vesicles Derived from Adipose Tissue Prevent Bisphosphonate-Related Osteonecrosis of the Jaw by Promoting Angiogenesis.International journal of nanomedicine · 2021Article
- The Case of Medication-Related Osteonecrosis of the Jaw Addressed from a Pathogenic Point of View. Innovative Therapeutic Strategies: Focus on the Most Recent Discoveries on Oral Mesenchymal Stem Cell-Derived Exosomes.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Current Understanding of the Pathophysiology of Osteonecrosis of the Jaw.Current osteoporosis reports · 2018Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesSite-specific suppression of bone remodelling has been implicated in bisphosphonate-(BP)-related osteonecrosis of the jaws (BRONJ). Due to the origin of jaw bone from cranial neural crest, osseous differentiation is regulated specifically by the antagonizing BMP-2-downstream-transcription factors Msx-1 and Dlx-5. Osteopontin has been implicated in bone remodelling and angiogenesis. The osteoblast and osteoclast progenitor proliferation mediating Msx-1 has been demonstrated to be suppressed in BRONJ. In vitro BPs were shown to increase Dlx-5 and to suppress osteopontin expression. This study targeted Dlx-5 and osteopontin in BRONJ-related and BP-exposed jaw bone compared with healthy jaw bone samples at protein- and messenger RNA (mRNA) level, since increased Dlx-5 and suppressed osteopontin might account for impaired bone turnover in BRONJ. MATERIALS AND
methodsFifteen BRONJ-exposed, 15 BP-exposed and 20 healthy jaw bone samples were processed for real-time reverse transcription polymerase chain reaction (RT-PCR) and for immunohistochemistry. Targeting Dlx-5, osteopontin and glyceraldehyde 3-phosphate dehydrogenase mRNA was extracted, quantified by the LabChip-method, followed by quantitative RT-PCR. For immunohistochemistry, an autostaining-based alkaline phosphatase antialkaline phosphatase (APAPP) staining kit was used. Semiquantitative assessment was performed measuring the ratio of stained cells/total number of cells (labelling index, Bonferroni adjustment).
resultsThe labelling index was significant decreased for osteopontin (p < 0.017) and significantly increased for Dlx-5 (p < 0.021) in BRONJ samples. In BRONJ specimens, a significant fivefold decrease in gene expression for osteopontin (p < 0.015) and a significant eightfold increase in Dlx-5 expression (p < 0.012) were found.
conclusionsBRONJ-related suppression of bone turnover is consistent with increased Dlx-5 expression and with suppression of osteopontin. The BP-related impaired BMP-2-Msx-1-Dlx-5 axis might explain the jaw bone specific alteration by BP. CLINICAL RELEVANCE: The findings of this study help to explain the restriction of RONJ to craniofacial bones. BRONJ might serve as a model of disease elucidating the specific signal transduction of neural crest cell-derived bone structures in health and disease.
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