ArticlePloS one2016
TLR4 Activation Promotes Bone Marrow MSC Proliferation and Osteogenic Differentiation via Wnt3a and Wnt5a Signaling.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 110 citations in OpenAlex.
- Effects ofInternational journal of environmental research and public health · 2022Trial
- Immunomodulatory effects of TAK-242 on osteogenesis of mesenchymal stem cells in acute inflammatory conditions.BMC molecular and cell biology · 2026Article
- Development of pyrogen-free utensils for cell culture by combining ozone/hydrogen peroxide mixed gas sterilization with steam-washing technology.Regenerative therapy · 2025Article
- Lipid-Driven Immunometabolism in Mesenchymal Stromal Cells: A New Axis for Musculoskeletal Regeneration.International journal of molecular sciences · 2025Review
- Impact of sepsis on bone marrow mesenchymal stem cells and its implications for hematopoiesis and immunosuppression.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- DAMPs, PAMPs, NLRs, RIGs, CLRs and TLRs - Understanding the Alphabet Soup in the Context of Bone Biology.Current osteoporosis reports · 2025Review
- Crab shell polypeptides enhance calcium dynamics and osteogenic activity in osteoporosis.Frontiers in pharmacology · 2025Article
- ERS-PERK Pathway is Involved in the Repair of the Pulpo-Dentinal Complex Under an Inflammatory Microenvironment.Stem cells international · 2025Article
- Transplantation of Wnt5a-modified Bone Marrow Mesenchymal Stem Cells Promotes Recovery After Spinal Cord Injury via the PI3K/AKT Pathway.Molecular neurobiology · 2024Article
- The Role of Protein Kinase C During the Differentiation of Stem and Precursor Cells into Tissue Cells.Biomedicines · 2024Review
- Lovastatin Combination Therapy Increases the Survival and Proliferation of Rat Bone Marrow-Derived Mesenchymal Stem Cells Against the Inflammatory Activity of Lipopolysaccharide.Cell biochemistry and biophysics · 2024Article
- Recent Advances in Hydrogel Technology in Delivering Mesenchymal Stem Cell for Osteoarthritis Therapy.Biomolecules · 2024Review
- TAZ reverses the inhibitory effects of LPS on the osteogenic differentiation of human periodontal ligament stem cells through the NF-κB signaling pathway.BMC oral health · 2024Article
- Expansion of human umbilical cord derived mesenchymal stem cells in regenerative medicine.World journal of stem cells · 2024Article
- Anti-tumorigenic effects of naive and TLR4-primed adipose-derived mesenchymal stem cells on pancreatic ductal adenocarcinoma cells.Cancer medicine · 2024Article
- Unraveling the potential of 3D bioprinted immunomodulatory materials for regulating macrophage polarization: State-of-the-art in bone and associated tissue regeneration.Bioactive materials · 2023Review
- The bone marrow side of axial spondyloarthritis.Nature reviews. Rheumatology · 2023Review
- Progress of Wnt Signaling Pathway in Osteoporosis.Biomolecules · 2023Review
- BAL Proteomic Signature of Lung Adenocarcinoma in IPF Patients and Its Transposition in Serum Samples for Less Invasive Diagnostic Procedures.International journal of molecular sciences · 2023Article
- Biglycan as a mediator of proinflammatory response and target for MDS and sAML therapy.Oncoimmunology · 2023Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mesenchymal stem cells (MSCs) from adult bone marrow maintain their self-renewal ability and the ability to differentiate into osteoblast. Thus, adult bone marrow MSCs play a key role in the regeneration of bone tissue. Previous studies indicated that TLR4 is expressed in MSCs and is critical in regulating the fate decision of MSCs. However, the exact functional role and underlying mechanisms of how TLR4 regulate bone marrow MSC proliferation and differentiation are unclear. Here, we found that activated TLR4 by its ligand LPS promoted the proliferation and osteogenic differentiation of MSCs in vitro. TLR4 activation by LPS also increased cytokine IL-6 and IL-1β production in MSCs. In addition, LPS treatment has no effect on inducing cell death of MSCs. Deletion of TLR4 expression in MSCs completely eliminated the effects of LPS on MSC proliferation, osteogenic differentiation and cytokine production. We also found that the mRNA and protein expression of Wnt3a and Wnt5a, two important factors in regulating MSC fate decision, was upregulated in a TLR4-dependent manner. Silencing Wnt3a with specific siRNA remarkably inhibited TLR4-induced MSC proliferation, while Wnt5a specific siRNA treatment significantly antagonized TLR4-induced MSC osteogenic differentiation. These results together suggested that TLR4 regulates bone marrow MSC proliferation and osteogenic differentiation through Wnt3a and Wnt5a signaling. These finding provide new data to understand the role and the molecular mechanisms of TLR4 in regulating bone marrow MSC functions. These data also provide new insight in developing new therapy in bone regeneration using MSCs by modulating TLR4 and Wnt signaling activity.
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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.