ArticlePloS one2012
Monocytes induce STAT3 activation in human mesenchymal stem cells to promote osteoblast formation.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers.
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Who cites it
119 citing papers in PubMed, 240 citations in OpenAlex.
- Commensal microbiota-coated biohybrid implants induce antibiofilm, osteogenic, and immunomodulatory responses in a human 3D immunocompetent model.Bioactive materials · 2026Article
- The enhanced osteogenic differentiation of human periodontal ligament stem cells and M2 polarization of macrophages may be mediated by EphB4/ephrinB2 signaling pathway: a study of their direct co-culture.Stem cell research & therapy · 2026Article
- Advances in the mechanism for steroid-induced osteonecrosis of the femoral head.Bone research · 2026Review
- Low-inflammatory macrophage-BMSC crosstalk enhances osteogenesis with attenuation of oxidative stress.American journal of clinical and experimental immunology · 2026Article
- Advances in the application and research of biomaterials in promoting bone repair and regeneration through immune modulation.Materials today. Bio · 2025Review
- Bu Yang Huan Wu Prevents Osteogenic Effect of Muscle-Derived Stromal Cells via Regulating JAK/STAT Pathway.Journal of cellular and molecular medicine · 2025Article
- Co-stimulation with equibiaxial strain and pre-osteoblast co-culture differentiates monocytes in a bone model.MRS communications · 2025Article
- Nobiletin promotes fracture healing by modulating macrophage polarization: a review.Frontiers in pharmacology · 2025Review
- Exosomal miR-1a-3p derived from glucocorticoid-stimulated M1 macrophages promotes the adipogenic differentiation of BMSCs in glucocorticoid-associated osteonecrosis of the femoral head by targeting Cebpz.Journal of nanobiotechnology · 2024Article
- Hdac3 deficiency limits periosteal reaction associated with Western diet feeding in female mice.Journal of cellular and molecular medicine · 2024Article
- Induction of osteoblast apoptosis stimulates macrophage efferocytosis and paradoxical bone formation.Bone research · 2024Article
- M2 Macrophages Guide Periosteal Stromal Cell Recruitment and Initiate Bone Injury Regeneration.Biomedicines · 2024Article
- Trained innate immunity modulates osteoblast and osteoclast differentiation.Stem cell reviews and reports · 2024Article
- Oncostatin M: Dual Regulator of the Skeletal and Hematopoietic Systems.Current osteoporosis reports · 2024Review
- Ketorolac and bone healing: a review of the basic science and clinical literature.European journal of orthopaedic surgery & traumatology : orthopedie traumatologie · 2024Review
- Disulfidptosis-related Protein RPN1 may be a Novel Anti-osteoporosis Target of Kaempferol.Combinatorial chemistry & high throughput screening · 2024Article
- Temporal dynamics of immune-stromal cell interactions in fracture healing.Frontiers in immunology · 2024Review
- Effect of Er:YAG Pulsed Laser-Deposited Hydroxyapatite Film on Titanium Implants on M2 Macrophage Polarization In Vitro and Osteogenesis In Vivo.International journal of molecular sciences · 2023Article
- Influences of Aged Bone Marrow Macrophages on Skeletal Health and Senescence.Current osteoporosis reports · 2023Review
- Betaine regulates adipogenic and osteogenic differentiation of hAD-MSCs.Molecular biology reports · 2023Article
59 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
A major therapeutic challenge is how to replace bone once it is lost. Bone loss is a characteristic of chronic inflammatory and degenerative diseases such as rheumatoid arthritis and osteoporosis. Cells and cytokines of the immune system are known to regulate bone turnover by controlling the differentiation and activity of osteoclasts, the bone resorbing cells. However, less is known about the regulation of osteoblasts (OB), the bone forming cells. This study aimed to investigate whether immune cells also regulate OB differentiation. Using in vitro cell cultures of human bone marrow-derived mesenchymal stem cells (MSC), it was shown that monocytes/macrophages potently induced MSC differentiation into OBs. This was evident by increased alkaline phosphatase (ALP) after 7 days and the formation of mineralised bone nodules at 21 days. This monocyte-induced osteogenic effect was mediated by cell contact with MSCs leading to the production of soluble factor(s) by the monocytes. As a consequence of these interactions we observed a rapid activation of STAT3 in the MSCs. Gene profiling of STAT3 constitutively active (STAT3C) infected MSCs using Illumina whole human genome arrays showed that Runx2 and ALP were up-regulated whilst DKK1 was down-regulated in response to STAT3 signalling. STAT3C also led to the up-regulation of the oncostatin M (OSM) and LIF receptors. In the co-cultures, OSM that was produced by monocytes activated STAT3 in MSCs, and neutralising antibodies to OSM reduced ALP by 50%. These data indicate that OSM, in conjunction with other mediators, can drive MSC differentiation into OB. This study establishes a role for monocyte/macrophages as critical regulators of osteogenic differentiation via OSM production and the induction of STAT3 signalling in MSCs. Inducing the local activation of STAT3 in bone cells may be a valuable tool to increase bone formation in osteoporosis and arthritis, and in localised bone remodelling during fracture repair.
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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.