ArticleFrontiers in cell and developmental biology2021
Acid-Induced Inflammatory Cytokines in Osteoblasts: A Guided Path to Osteolysis in Bone Metastasis.
Article in Frontiers in cell and developmental biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 15 citations in OpenAlex.
- Decoding triple negative breast cancer bone metastasis: from 3D bioprinted models to clinical translation.Journal of nanobiotechnology · 2026Review
- Modeling and targeting the hostile physicochemical niche in bone metastasis: from experimental platforms to niche-directed therapy.Frontiers in cell and developmental biology · 2026Review
- Research advances in the role of osteoblasts and their derivatives in the development, recurrence, and distant metastasis of malignant bone tumors: a narrative review.EFORT open reviews · 2025Review
- Article
- High-fat diet-induced osteoporosis in mice under hypoxic conditions.BMC musculoskeletal disorders · 2025Article
- Balancing the Scales: The Dual Role of Interleukins in Bone Metastatic Microenvironments.International journal of molecular sciences · 2024Review
- Muscle and Bone Defects in Metastatic Disease.Current osteoporosis reports · 2022Review
- Radiodynamic Therapy with Acridine Orange Is an Effective Treatment for Bone Metastases.Biomedicines · 2022Article
- Effects of the Interleukin-6 Receptor Blocker Sarilumab on Metabolic Activity and Differentiation Capacity of Primary Human Osteoblasts.Pharmaceutics · 2022Article
- Photoluminescent carbon dots (PCDs) from sour apple: a biocompatible nanomaterial for preventing UHMWPE wear-particle induced osteolysis via modulating Chemerin/ChemR23 and SIRT1 signaling pathway and its bioimaging application.Journal of nanobiotechnology · 2022Article
- Dickkopf‑3 and β‑catenin play opposite roles in the Wnt/β‑catenin pathway during the abnormal subchondral bone formation of human knee osteoarthritis.International journal of molecular medicine · 2022Article
- Osteoporosis in Patients With Respiratory Diseases.Frontiers in physiology · 2022Review
- Acid Microenvironment in Bone Sarcomas.Cancers · 2021Review
- Chemerin/ChemR23 signaling mediates the effects of ultra-high molecular weight polyethylene wear particles on the balance between osteoblast and osteoclast differentiation.Annals of translational medicine · 2021Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bone metastasis (BM) is a dismal complication of cancer that frequently occurs in patients with advanced carcinomas and that often manifests as an osteolytic lesion. In bone, tumor cells promote an imbalance in bone remodeling via the release of growth factors that, directly or indirectly, stimulate osteoclast resorption activity. However, carcinoma cells are also characterized by an altered metabolism responsible for a decrease of extracellular pH, which, in turn, directly intensifies osteoclast bone erosion. Here, we speculated that tumor-derived acidosis causes the osteoblast-osteoclast uncoupling in BM by modulating the pro-osteoclastogenic phenotype of osteoblasts. According to our results, a low pH recruits osteoclast precursors and promotes their differentiation through the secretome of acid-stressed osteoblasts that includes pro-osteoclastogenic factors and inflammatory mediators, such as RANKL, M-CSF, TNF, IL-6, and, above the others, IL-8. The treatment with the anti-IL-6R antibody tocilizumab or with an anti-IL-8 antibody reverted this effect. Finally, in a series of BM patients, circulating levels of the osteolytic marker TRACP5b significantly correlated with IL-8. Our findings brought out that tumor-derived acidosis promotes excessive osteolysis at least in part by inducing an inflammatory phenotype in osteoblasts, and these results strengthen the use of anti-IL-6 or anti-IL-8 strategies to treat osteolysis in BM.
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