ArticleThe Journal of biological chemistry2010
Synergism between Wnt3a and heparin enhances osteogenesis via a phosphoinositide 3-kinase/Akt/RUNX2 pathway.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 1 citations in OpenAlex.
- From passive fillers to active implants: A 3D-printed trilayer piezoelectric scaffold recapitulating native bone hierarchy.Bioactive materials · 2027Article
- Heparan sulfate as a central modulator of growth factor dynamics in tissue regeneration.APL bioengineering · 2025Article
- Mechanistic studies of chondroitin sulfate/dermatan sulfate isolated from freshwater fish discards on osteogenesis in MC3T3-E1 cells.Glycoconjugate journal · 2025Article
- The circulatory levels and bone expression of MIR21, 34a, 155 and their target genes in a section of Egyptian Population.Scientific reports · 2024Article
- Bone marrow mesenchymal stem cells overexpressing stromal cell- derived factor 1 aid in bone formation in osteoporotic mice.BMC musculoskeletal disorders · 2024Article
- Adipose-derived mesenchymal stem cell therapy for connective tissue diseases and complications.Inflammation and regeneration · 2024Review
- Glycobiology in osteoclast differentiation and function.Bone research · 2023Review
- P-15 promotes chondrocyte proliferation in osteoarthritis by regulating SFPQ to target the Akt-RUNX2 axis.Journal of orthopaedic surgery and research · 2023Article
- Mesenchymal stem cells and macrophages and their interactions in tendon-bone healing.Journal of orthopaedic translation · 2023Review
- Human bone marrow stromal cells: the impact of anticoagulants on stem cell properties.Frontiers in cell and developmental biology · 2023Article
- Reversing the imbalance in bone homeostasis via sustained release of SIRT-1 agonist to promote bone healing under osteoporotic condition.Bioactive materials · 2023Article
- Surface Engineering of Auxetic Scaffolds for Neural and Vascular Differentiation from Human Pluripotent Stem Cells.Advanced healthcare materials · 2023Article
- Regulation of stem cell fate by HSPGs: implication in hair follicle cycling.NPJ Regenerative medicine · 2022Review
- Therapeutic effects of adipose-derived mesenchymal stem/stromal cells with enhanced migration ability and hepatocyte growth factor secretion by low-molecular-weight heparin treatment in bleomycin-induced mouse models of systemic sclerosis.Arthritis research & therapy · 2022Article
- Melatonin and the Programming of Stem Cells.International journal of molecular sciences · 2022Review
- Effects of carrier solutions on the viability and efficacy of canine adipose-derived mesenchymal stem cells.BMC veterinary research · 2022Article
- The Auxiliary Role of Heparin in Bone Regeneration and its Application in Bone Substitute Materials.Frontiers in bioengineering and biotechnology · 2022Review
- SHIP1 Activator AQX-1125 Regulates Osteogenesis and Osteoclastogenesis Through PI3K/Akt and NF-κb Signaling.Frontiers in cell and developmental biology · 2022Article
- Long-term effect of hematopoietic cell transplantation on systemic inflammation in patients with mucopolysaccharidoses.Blood advances · 2021Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
A new strategy has emerged to improve healing of bone defects using exogenous glycosaminoglycans by increasing the effectiveness of bone-anabolic growth factors. Wnt ligands play an important role in bone formation. However, their functional interactions with heparan sulfate/heparin have only been investigated in non-osseous tissues. Our study now shows that the osteogenic activity of Wnt3a is cooperatively stimulated through physical interactions with exogenous heparin. N-Sulfation and to a lesser extent O-sulfation of heparin contribute to the physical binding and optimal co-stimulation of Wnt3a. Wnt3a-heparin signaling synergistically increases osteoblast differentiation with minimal effects on cell proliferation. Thus, heparin selectively reduces the effective dose of Wnt3a needed to elicit osteogenic, but not mitogenic responses. Mechanistically, Wnt3a-heparin signaling strongly activates the phosphoinositide 3-kinase/Akt pathway and requires the bone-related transcription factor RUNX2 to stimulate alkaline phosphatase activity, which parallels canonical beta-catenin signaling. Collectively, our findings establish the osteo-inductive potential of a heparin-mediated Wnt3a-phosphoinositide 3-kinase/Akt-RUNX2 signaling network and suggest that heparan sulfate supplementation may selectively reduce the therapeutic doses of peptide factors required to promote bone formation.
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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.