ArticleJournal of translational medicine2019
Osteoclastic expression of higher-level regulators NFATc1 and BCL6 in medication-related osteonecrosis of the jaw secondary to bisphosphonate therapy: a comparison with osteoradionecrosis and osteomyelitis.
Article in Journal of translational medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 37 citations in OpenAlex.
- Enhancement of Orthodontic Tooth Movement by Oral Administration of Pangasius hypophthalmus Oil: An In Vivo Study.Orthodontics & craniofacial research · 2026Article
- Molecular Basis of Surfactin-Induced Macrophage Modulation and Its Implications in Medication-Related Osteonecrosis of the Jaw Pathogenesis.International journal of molecular sciences · 2026Article
- Dual-functional micro- to nano-CFR-PEEK: promoting Hippo-mediated osseointegration while inhibitingRegenerative biomaterials · 2026Article
- Targeted drug repurposing in medication-related osteonecrosis of the jaw: a review of teriparatide and pentoxifylline/α-tocopherol protocols.Frontiers in medicine · 2026Review
- Involvement of resistant bacteria in the severity of refractory osteonecrosis of the jaw.Clinical oral investigations · 2025Article
- Article
- Medication-related osteonecrosis of the jaws: a series of 22 cases highlighting their histopathological features.Brazilian oral research · 2025Article
- A potential function for MicroRNA-124 in normal and pathological bone conditions.Non-coding RNA research · 2024Review
- The Involvement of microRNAs in Bone Remodeling Signaling Pathways and Their Role in the Development of Osteoporosis.Biology · 2024Review
- Article
- Bisphosphonates and Their Connection to Dental Procedures: Exploring Bisphosphonate-Related Osteonecrosis of the Jaws.Cancers · 2023Review
- Medication-related osteonecrosis of the jaw without osteolysis on computed tomography: a retrospective and observational study.Scientific reports · 2023Observational
- Gingival Mesenchymal Stem Cells Metabolite Decreasing TRAP, NFATc1, and Sclerostin Expression in LPS-Associated Inflammatory Osteolysis In Vivo.European journal of dentistry · 2023Article
- Medication-Related Osteonecrosis: Why the Jawbone?Dentistry journal · 2023Review
- Ineffectiveness of Antiresorptive Agent Drug Holidays in Osteoporosis Patients for Treatment of Medication-Related Osteonecrosis of the Jaw: Consideration from Immunohistological Observation of Osteoclast Suppression and Treatment Outcomes.International journal of environmental research and public health · 2022Article
- Article
- Zoledronate Causes a Systemic Shift of Macrophage Polarization towards M1 In Vivo.International journal of molecular sciences · 2021Article
- Comprehensive analysis of Transcription Factors identified novel prognostic biomarker in human bladder cancer.Journal of Cancer · 2021Article
- Suppressive effects of an apoptotic mimicry prepared from jumbo-flying squid-skin phospholipids on the osteoclastogenesis in receptor activator of nuclear factor kappa B ligand/macrophage colony-stimulating factor-induced RAW 264.7 cells.Journal of the Chinese Medical Association : JCMA · 2021Article
- From Osteoclast Differentiation to Osteonecrosis of the Jaw: Molecular and Clinical Insights.International journal of molecular sciences · 2019Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWith an increasing indication spectrum of antiresorptive drugs, the medication-related osteonecrosis of the jaw secondary to bisphosphonate therapy [MRONJ (BP)] is continuously gaining clinical relevance. Impaired osteoclast function, accompanied by altered cell morphology and expression of osteoclastic effector proteins, contributes to the pathogenesis of MRONJ (BP). However, the underlying regulatory mechanisms at a transcriptional level are unaddressed so far. These mechanisms are crucial to the development of disease-characteristic osteoclastic anomalies, that contribute to the pathogenesis of MRONJ (BP). NFATc1 is considered a master upstream osteoclastic activator, whereas BCL6 acts as osteoclastic suppressor. The present study aimed to elucidate the NFATc1 and BCL6 mediated osteoclastic regulation and activity in MRONJ (BP) compared to osteoradionecrosis (ORN) and osteomyelitis (OM) and normal jaw bone.
methodsFormalin-fixed jaw bone specimens from 70 patients [MRONJ (BP) n = 30; OM: n = 15, ORN: n = 15, control: n = 10] were analyzed retrospectively for osteoclast expression of NFATc1 and BCL6. The specimens were processed for H&E staining and immunohistochemistry. The histological sections were digitalized and analyzed by virtual microscopy.
resultsOsteoclastic expression of NFATc1 and BCL6 was significantly higher in MRONJ (BP) specimens compared to OM and control specimens. NFATc1 and BCL6 labeling indices revealed no significant differences between MRONJ (BP) and ORN. The ratio of nuclear BCL6+ osteoclasts to cytoplasmic BCL6+ osteoclasts revealed significantly higher values for MRONJ (BP) specimens compared to OM and controls.
conclusionThis study displays that osteoclasts in MRONJ (BP) tissues feature increased expression of the higher-level regulators, paradoxically of both NFATc1 and BCL6. These observations can help to explain the genesis of morphologically altered and resorptive inactive osteoclasts in MRONJ (BP) tissues by outlining the transcriptional regulation of the pathomechanically relevant osteoclastic effector proteins. Furthermore, they strengthen the etiological delineation of MRONJ (BP) from OM and extend the osteoclast profiles of MRONJ (BP), OM and ORN and thus could lead to a better histopathological differentiation that can improve treatment decision and motivate new therapeutic concepts.
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