ArticleInternational journal of molecular sciences2016
Unfractionated Heparin Promotes Osteoclast Formation in Vitro by Inhibiting Osteoprotegerin Activity.
Article in International journal of molecular sciences, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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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.
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Who cites it
13 citing papers in PubMed, 26 citations in OpenAlex.
- Mineral and Bone Disease in CKD and Kidney Transplantation: Controversies, Gaps, and a Path Forward.Kidney international reports · 2026Review
- Effects of pregnancy and lactation-associated osteoporosis on children: analysis using linked mother and child data.Journal of bone and mineral metabolism · 2026Article
- The Effect of Heparin on Bone Metabolism and Orthodontic Tooth Movement in Rats.Clinical and experimental dental research · 2025Article
- Glycobiology in osteoclast differentiation and function.Bone research · 2023Review
- Dilemmas in the Choice of Adequate Therapeutic Treatment in Patients with Acute Pulmonary Embolism-From Modern Recommendations to Clinical Application.Pharmaceuticals (Basel, Switzerland) · 2022Review
- STAT3-mediated osteogenesis and osteoclastogenesis in osteoporosis.Cell communication and signaling : CCS · 2022Review
- The Auxiliary Role of Heparin in Bone Regeneration and its Application in Bone Substitute Materials.Frontiers in bioengineering and biotechnology · 2022Review
- Triple Culture of Primary Human Osteoblasts, Osteoclasts and Osteocytes as an In Vitro Bone Model.International journal of molecular sciences · 2021Article
- Effect of long-term use of unfractionated or low-molecular-weight heparin on bone mineral density in maintenance hemodialysis patients.Hemodialysis international. International Symposium on Home Hemodialysis · 2020Article
- Different type and dosage of heparin were not associated with the progression of coronary artery calcification in haemodialysis patients.Nephrology (Carlton, Vic.) · 2020Article
- The Role of Mast Cells in Bone Metabolism and Bone Disorders.Frontiers in immunology · 2020Review
- Osteoblastic heparan sulfate glycosaminoglycans control bone remodeling by regulating Wnt signaling and the crosstalk between bone surface and marrow cells.Cell death & disease · 2017Article
- Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heparin has been proven to enhance bone resorption and induce bone loss. Since osteoclasts play a pivotal role in bone resorption, the effect of heparin on osteoclastogenesis needs to be clarified. Since osteocytes are the key modulator during osteoclastogenesis, we evaluated heparin's effect on osteoclastogenesis in vitro by co-culturing an osteocyte cell line (MLO-Y4) and pre-osteoclasts (RAW264.7). In this co-culture system, heparin enhanced osteoclastogenesis and osteoclastic bone resorption while having no influence on the production of RANKL (receptor activator of NFκB ligand), M-CSF (macrophage colony-stimulating factor), and OPG (osteoprotegerin), which are three main regulatory factors derived from osteocytes. According to previous studies, heparin could bind specifically to OPG and inhibit its activity, so we hypothesized that this might be a possible mechanism of heparin activity. To test this hypothesis, osteoclastogenesis was induced using recombinant RANKL or MLO-Y4 supernatant. We found that heparin has no effect on RANKL-induced osteoclastogenesis (contains no OPG). However, after incubation with OPG, the capacity of MLO-Y4 supernatant for supporting osteoclast formation was increased. This effect disappeared after OPG was neutralized and reappeared after OPG was replenished. These results strongly suggest that heparin promotes osteocyte-modulated osteoclastogenesis in vitro, at least partially, through inhibiting OPG activity.
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