ArticleCancer research2016
Bidirectional Notch Signaling and Osteocyte-Derived Factors in the Bone Marrow Microenvironment Promote Tumor Cell Proliferation and Bone Destruction in Multiple Myeloma.
Article in Cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 133 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
133 citing papers in PubMed, 210 citations in OpenAlex.
- Article
- Continuous multi-omics pathway enrichment analysis resolves hidden functional heterogeneity.Briefings in bioinformatics · 2026Article
- Osteocytes in the Metastatic Bone Niche: Mechanistic Pathways and Therapeutic Targets.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Engineered bone matrix models for understanding breast cancer skeletal metastasis.Cancer metastasis reviews · 2026Review
- Bone-modifying therapy in multiple myeloma: a comprehensive review.Frontiers in oncology · 2026Review
- The Crosstalk Between B Cells and the Skeletal System During Development, Aging, and in Pathological Conditions.Current osteoporosis reports · 2025Review
- Mesenchymal Stem Cells in Socket Healing and MRONJ.Orthodontics & craniofacial research · 2025Review
- Romosozumab in postmenopausal women with smoldering multiple myeloma: a prospective 12-mo study.JBMR plus · 2025Article
- Healing of lytic lesions and restoration of bone health in multiple myeloma through sclerostin inhibition.Experimental hematology & oncology · 2025Article
- Review
- Article
- A novel CCL3-HMGB1 signaling axis regulating osteocyte RANKL expression in multiple myeloma.Haematologica · 2025Article
- Mechanistic insights into bone destruction in multiple myeloma: Cellular and molecular perspectives.Journal of bone oncology · 2025Review
- Article
- 2D and 3D In Vitro Co-culture for Cancer and Bone Cell Interaction Studies.Methods in molecular biology (Clifton, N.J.) · 2025Article
- 2D and 3D In Vitro Co-culture for Cancer and Bone Cell Interaction Studies.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Bone health in cancer: perspective on the use of osteoanabolic agents.Therapeutic advances in endocrinology and metabolism · 2025Review
- Single-Cell Transcriptomic Analysis Identifies Senescent Osteocytes That Trigger Bone Destruction in Breast Cancer Metastasis.Cancer research · 2024Article
- Relationship between adipocytes and hematological tumors in the bone marrow microenvironment: a literature review.Translational cancer research · 2024Review
- Evidence for peri-lacunar remodeling and altered osteocyte lacuno-canalicular network in mouse models of myeloma-induced bone disease.JBMR plus · 2024Article
73 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
In multiple myeloma, an overabundance of monoclonal plasma cells in the bone marrow induces localized osteolytic lesions that rarely heal due to increased bone resorption and suppressed bone formation. Matrix-embedded osteocytes comprise more than 95% of bone cells and are major regulators of osteoclast and osteoblast activity, but their contribution to multiple myeloma growth and bone disease is unknown. Here, we report that osteocytes in a mouse model of human MM physically interact with multiple myeloma cells in vivo, undergo caspase-3-dependent apoptosis, and express higher RANKL (TNFSF11) and sclerostin levels than osteocytes in control mice. Mechanistic studies revealed that osteocyte apoptosis was initiated by multiple myeloma cell-mediated activation of Notch signaling and was further amplified by multiple myeloma cell-secreted TNF. The induction of apoptosis increased osteocytic Rankl expression, the osteocytic Rankl/Opg (TNFRSF11B) ratio, and the ability of osteocytes to attract osteoclast precursors to induce local bone resorption. Furthermore, osteocytes in contact with multiple myeloma cells expressed high levels of Sost/sclerostin, leading to a reduction in Wnt signaling and subsequent inhibition of osteoblast differentiation. Importantly, direct contact between osteocytes and multiple myeloma cells reciprocally activated Notch signaling and increased Notch receptor expression, particularly Notch3 and 4, stimulating multiple myeloma cell growth. These studies reveal a previously unknown role for bidirectional Notch signaling that enhances MM growth and bone disease, suggesting that targeting osteocyte-multiple myeloma cell interactions through specific Notch receptor blockade may represent a promising treatment strategy in multiple myeloma.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.