ArticlePloS one2013
High throughput transcriptome profiling of lithium stimulated human mesenchymal stem cells reveals priming towards osteoblastic lineage.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 65 citations in OpenAlex.
- Unveiling the Mysteries of CLEC3B: Physiological Roles, Pathological Impacts, and Research Gaps.Cells · 2026Review
- Decreased expression of GEM in osteoarthritis cartilage regulates chondrogenic differentiation via Wnt/β-catenin signaling.Journal of orthopaedic surgery and research · 2023Article
- Li-Doped Bioactive Ceramics: Promising Biomaterials for Tissue Engineering and Regenerative Medicine.Journal of functional biomaterials · 2022Review
- Exopolysaccharide of Enterococcus faecium L15 promotes the osteogenic differentiation of human dental pulp stem cells via p38 MAPK pathway.Stem cell research & therapy · 2022Article
- Competitive Hybridization of a Microarray Identifies CMKLR1 as an Up-Regulated Gene in Human Bone Marrow-Derived Mesenchymal Stem Cells Compared to Human Embryonic Fibroblasts.Current issues in molecular biology · 2022Article
- Osteogenic ability using porous hydroxyapatite scaffold-based delivery of human placenta-derived mesenchymal stem cells.Experimental and therapeutic medicine · 2021Article
- The preconditioning of lithium promotes mesenchymal stem cell-based therapy for the degenerated intervertebral disc via upregulating cellular ROS.Stem cell research & therapy · 2021Article
- Repair of segmental bone defect using tissue engineered heterogeneous deproteinized bone doped with lithium.Scientific reports · 2021Article
- Inhibition of mitochondrial complex II in neuronal cells triggers unique pathways culminating in autophagy with implications for neurodegeneration.Scientific reports · 2021Article
- Serum Amyloid A Correlates With the Osteonecrosis of Femoral Head by Affecting Bone Metabolism.Frontiers in pharmacology · 2021Article
- Comparative analysis of differentially secreted proteins in serum-free and serum-containing media by using BONCAT and pulsed SILAC.Scientific reports · 2019Article
- Cationic Substitutions in Hydroxyapatite: Current Status of the Derived Biofunctional Effects and Their In Vitro Interrogation Methods.Materials (Basel, Switzerland) · 2018Review
- Bioactive Glasses: Where Are We and Where Are We Going?Journal of functional biomaterials · 2018Review
- Applications of Metals for Bone Regeneration.International journal of molecular sciences · 2018Review
- Rad GTPase is essential for the regulation of bone density and bone marrow adipose tissue in mice.Bone · 2017Article
- In Vitro Human Umbilical Vein Endothelial Cells Response to Ionic Dissolution Products from Lithium-Containing 45S5 Bioactive Glass.Materials (Basel, Switzerland) · 2017Article
- Environmental Factors Impacting Bone-Relevant Chemokines.Frontiers in endocrinology · 2017Article
- Lithium prevents rat steroid-related osteonecrosis of the femoral head by β-catenin activation.Endocrine · 2016Article
- Modeling the Pro-inflammatory Tumor Microenvironment in Acute Lymphoblastic Leukemia Predicts a Breakdown of Hematopoietic-Mesenchymal Communication Networks.Frontiers in physiology · 2016Article
- Increased expression of chemerin in squamous esophageal cancer myofibroblasts and role in recruitment of mesenchymal stromal cells.PloS one · 2014Article
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
Human mesenchymal stem cells (hMSCs) present in the bone marrow are the precursors of osteoblasts, chondrocytes and adipocytes, and hold tremendous potential for osteoregenerative therapy. However, achieving directed differentiation into osteoblasts has been a major concern. The use of lithium for enhancing osteogenic differentiation has been documented in animal models but its effect in humans is not clear. We, therefore, performed high throughput transcriptome analysis of lithium-treated hMSCs to identify altered gene expression and its relevance to osteogenic differentiation. Our results show suppression of proliferation and enhancement of alkaline phosphatase (ALP) activity upon lithium treatment of hMSCs under non-osteogenic conditions. Microarray profiling of lithium-stimulated hMSC revealed decreased expression of adipogenic genes (CEBPA, CMKLR1, HSD11B1) and genes involved in lipid biosynthesis. Interestingly, osteoclastogenic factors and immune responsive genes (IL7, IL8, CXCL1, CXCL12, CCL20) were also downregulated. Negative transcriptional regulators of the osteogenic program (TWIST1 and PBX1) were suppressed while genes involved in mineralization like CLEC3B and ATF4 were induced. Gene ontology analysis revealed enrichment of upregulated genes related to mesenchymal cell differentiation and signal transduction. Lithium priming led to enhanced collagen 1 synthesis and osteogenic induction of lithium pretreated MSCs resulted in enhanced expression of Runx2, ALP and bone sialoprotein. However, siRNA-mediated knockdown of RRAD, CLEC3B and ATF4 attenuated lithium-induced osteogenic priming, identifying a role for RRAD, a member of small GTP binding protein family, in osteoblast differentiation. In conclusion, our data highlight the transcriptome reprogramming potential of lithium resulting in higher propensity of lithium "primed" MSCs for osteoblastic differentiation.
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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.