ArticleBone2013
Heparanase inhibits osteoblastogenesis and shifts bone marrow progenitor cell fate in myeloma bone disease.
Article in Bone, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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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.
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Who cites it
28 citing papers in PubMed, 48 citations in OpenAlex.
- Changes in Bone Marrow Fat upon Dietary-Induced Weight Loss.Nutrients · 2020Trial
- Effect of bone marrow blood versus peripheral blood on the hemostatic balance of osteoblasts and endothelial cells.Scientific reports · 2025Article
- Mesenchymal stem cells lineage and their role in disease development.Molecular medicine (Cambridge, Mass.) · 2024Review
- Turning the spotlight on bone marrow adipocytes in haematological malignancy and non-malignant conditions.British journal of haematology · 2023Review
- Effect of HPSE and HPSE2 SNPs on the Risk of Developing Primary Paraskeletal Multiple Myeloma.Cells · 2023Article
- Runx2 Deficiency in Osteoblasts Promotes Myeloma Resistance to Bortezomib by Increasing TSP-1-Dependent TGFβ1 Activation and Suppressing Immunity in Bone Marrow.Molecular cancer therapeutics · 2022Article
- Role of heparinase in the gastrointestinal dysfunction of sepsis (Review).Experimental and therapeutic medicine · 2022Review
- Single-Cell Sequencing Analysis and Multiple Machine Learning Methods Identified G0S2 and HPSE as Novel Biomarkers for Abdominal Aortic Aneurysm.Frontiers in immunology · 2022Article
- Myeloma Bone Disease: The Osteoblast in the Spotlight.Journal of clinical medicine · 2021Review
- Bone Marrow Mesenchymal Stromal Cells in Multiple Myeloma: Their Role as Active Contributors to Myeloma Progression.Cancers · 2021Review
- Heparanase-enhanced Shedding of Syndecan-1 and Its Role in Driving Disease Pathogenesis and Progression.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2020Review
- Does exogenously adding heparanase accelerate bone healing?Journal of the Chinese Medical Association : JCMA · 2020Article
- Heparanase-1 facilitates bone remodeling on bone defect animal model with optimal dosage and treatment duration.Journal of the Chinese Medical Association : JCMA · 2020Article
- Myeloma cells shift osteoblastogenesis to adipogenesis by inhibiting the ubiquitin ligase MURF1 in mesenchymal stem cells.Science signaling · 2020Article
- Runx2 Deficiency in Osteoblasts Promotes Myeloma Progression by Altering the Bone Microenvironment at New Bone Sites.Cancer research · 2020Article
- Dynamic responses of the haematopoietic stem cell niche to diverse stresses.Nature cell biology · 2020Review
- Epigenetic-Based Mechanisms of Osteoblast Suppression in Multiple Myeloma Bone Disease.JBMR plus · 2019Review
- Surgical thyroparathyroidectomy prevents progression of 5TGM1 murine multiple myelomaJournal of bone oncology · 2018Review
- Demystifying the pH dependent conformational changes of human heparanase pertaining to structure-function relationships: an in silico approach.Journal of computer-aided molecular design · 2018Article
- [Research progress in osteogenesis and osteogenic mechanism of heparan sulfate].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2017Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
A major cause of morbidity in patients with multiple myeloma is the development and progression of bone disease. Myeloma bone disease is characterized by rampant osteolysis in the presence of absent or diminished bone formation. Heparanase, an enzyme that acts both at the cell-surface and within the extracellular matrix to degrade polymeric heparan sulfate chains, is upregulated in a variety of human cancers including multiple myeloma. We and others have shown that heparanase enhances osteoclastogenesis and bone loss. However, increased osteolysis is only one element of the spectrum of myeloma bone disease. In the present study, we hypothesized that heparanase would also affect mesenchymal cells in the bone microenvironment and investigated the effect of heparanase on the differentiation of osteoblast/stromal lineage cells. Using a combination of molecular, biochemical, cellular and in vivo approaches, we demonstrated that heparanase significantly inhibited osteoblast differentiation and mineralization, and reduced bone formation in vivo. In addition, heparanase shifts the differentiation potential of osteoblast progenitors from osteoblastogenesis to adipogenesis. Mechanistically, this shift in cell fate is due, at least in part, to heparanase-enhanced production and secretion of the Wnt signaling pathway inhibitor DKK1 by both osteoblast progenitors and myeloma cells. Collectively, these data provide important new insights into the role of heparanase in all aspects of myeloma bone disease and strongly support the use of heparanase inhibitors in the treatment of multiple myeloma.
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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.