ArticleInternational journal of molecular sciences2019
Zoledronate Enhances Osteocyte-Mediated Osteoclast Differentiation by IL-6/RANKL Axis.
Article in International journal of molecular sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 2 of them syntheses that pooled it.
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Who cites it
28 citing papers in PubMed, 2 syntheses or guidelines pooled it, 46 citations in OpenAlex.
- A Systematic Review of the Effects of Bisphosphonates on Osteoblasts In Vitro.Calcified tissue international · 2025Pooled it
- Comprehensive evaluation of compound Kushen injection combined with zoledronic acid in treating bone metastasis cancer pain based on meta-analysis and decision tree model.Frontiers in pain research (Lausanne, Switzerland) · 2024Pooled it
- Cell signaling and transcriptional regulation of osteoclast lineage commitment, differentiation, bone resorption and diseases.Cell discovery · 2026Review
- Advanced biomaterial-based approaches for medication-related osteonecrosis of the jaw.Open life sciences · 2026Article
- Mechanistic role of the IL-1β/c-Fos/NFATc1 signaling axis in echinococcal infection-promoted osteoclast differentiation and activation in pathological osteolysis: a prospective controlled trial.Journal of orthopaedic surgery and research · 2025Article
- Exercise-Mediated Skeletal Muscle-Derived IL-6 Regulates Bone Metabolism: A New Perspective on Muscle-Bone Crosstalk.Biomolecules · 2025Review
- Cell communication and relevant signaling pathways in osteogenesis-angiogenesis coupling.Bone research · 2025Review
- Inhibition of Bone Resorption and Anti-Inflammatory Effect of 7-Hydroxycoumarin in an Animal Model of Lipopolysaccharide-Induced Periodontal Disease.International journal of dentistry · 2025Article
- Antiresorptive medication-related osteonecrosis of the jaw: Incidence and preventive measures utilization in cancer patients.The Saudi dental journal · 2024Article
- Nitrogen-containing bisphosphonate induces enhancement of OPG expression and inhibition of RANKL expression via inhibition of farnesyl pyrophosphate synthase to inhibit the osteogenic differentiation and calcification in vascular smooth muscle cells.BMC cardiovascular disorders · 2024Article
- Article
- Predictive and prognostic biomarkers of bone metastasis in breast cancer: current status and future directions.Cell & bioscience · 2023Review
- Bisphosphonate-incorporated coatings for orthopedic implants functionalization.Materials today. Bio · 2023Review
- Gold-nanosphere mitigates osteoporosis through regulating TMAO metabolism in a gut microbiota-dependent manner.Journal of nanobiotechnology · 2023Article
- Drug discovery in spinal cord injury-induced osteoporosis: a text mining-based study.Annals of translational medicine · 2022Article
- Zoledronic acid inhibits osteoclastogenesis and bone resorptive function by suppressing RANKL‑mediated NF‑κB and JNK and their downstream signalling pathways.Molecular medicine reports · 2022Article
- Characterization of Mesenchymal Stem Cells Derived from Bisphosphonate-Related Osteonecrosis of the Jaw Patients' Gingiva.Stem cell reviews and reports · 2022Article
- Review
- The Role of the Immune Response in the Development of Medication-Related Osteonecrosis of the Jaw.Frontiers in immunology · 2021Review
- Inhibition Effect of Zoledronate on the Osteoclast Differentiation of RAW264.7 Induced by Titanium Particles.BioMed research international · 2021Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Bisphosphonates are one of the most widely used synthetic pyrophosphate analogues for the treatment of bone resorbing diseases such as osteoporosis, multiple myeloma, and bone metastases. Although the therapeutic usefulness of bisphosphonates mainly depends on their anti-osteoclastogenic effect, a severe side-effect of bisphosphonates called bisphosphonate-related osteonecrosis of the jaw (BRONJ) could not be explained by the anti-osteoclastogenic effect of bisphosphonates. In the present study, we have evaluated the changes in osteoclastogenesis- or osteoblastogenesis-supporting activities of osteocytes induced by bisphosphonates. Zoledronate, a nitrogen-containing bisphosphonate, markedly increased both the receptor activator of nuclear factor kB ligand (RANKL) as well as sclerostin in osteocyte-like MLO-Y4 cells, which were functionally revalidated by osteoclast/osteoblast generating activities of the conditioned medium obtained from zoledronate-treated MLO-Y4 cells. Of note, the zoledronate treatment-induced upregulation of the RANKL expression was mediated by autocrine interleukin-6 (IL-6) and subsequent activation of the signal transducer and activator of transcription 3 (STAT3) pathway. These results were evidenced by the blunted RANKL expression in the presence of a Janus activated kinase (JAK2)/STAT3 inhibitor, AG490. Also, the osteoclastogenesis-supporting activity was significantly decreased in zoledronate-treated MLO-Y4 cells in the presence of IL-6 neutralizing IgG compared to that of the control IgG. Thus, our results show previously unanticipated effects of anti-bone resorptive bisphosphonate and suggest a potential clinical importance of osteocytes in BRONJ development.
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