ArticleJournal of bone and mineral metabolism2014
IL-6 negatively regulates osteoblast differentiation through the SHP2/MEK2 and SHP2/Akt2 pathways in vitro.
Article in Journal of bone and mineral metabolism, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers, 1 of them a synthesis that pooled it.
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Who cites it
113 citing papers in PubMed, 1 synthesis or guideline pooled it, 213 citations in OpenAlex.
- The Use of Platelet-Rich Plasma for the Treatment of Osteonecrosis of the Femoral Head: A Systematic Review.BioMed research international · 2020Pooled it
- The regulatory significance of chondrocyte hypertrophy in maintaining chondrocyte homeostasis, regeneration and repair.Future science OA · 2026Review
- CSF1R+ macrophage and osteoclast depletion impairs neural crest proliferation and craniofacial morphogenesis.Development (Cambridge, England) · 2026Article
- Relationship between muscle FNDC5, FGF21 mRNA, miR-150 and bone loss after sciatic denervation.Journal of physiology and biochemistry · 2026Article
- GelMA Hydrogel Stiffness Modulates IL-6- and BMP-2-Induced Immune Dysregulation in Human Mesenchymal Stem Cells.Biomedicines · 2026Article
- Impact of oral glucocorticoids on the effectiveness of romosozumab: the multicenter OASIS cohort study.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2026Observational
- Bisphosphonate and statin: adverse effects of co-medication on wound healing in in vitro models of periodontal tissues.Acta odontologica Scandinavica · 2026Article
- The risk of osteoporosis in COPD: An analysis of sex differences and mediating effects based on NHANES.NPJ primary care respiratory medicine · 2026Article
- Stress-induced IL-6 regulation in pediatric bone growth disorders: current insights and therapeutic strategies.Frontiers in endocrinology · 2026Review
- Macrophage polarization regulates bone homeostasis: a potential etiology and therapy for postmenopausal osteoporosis.Frontiers in immunology · 2026Review
- Bio-OssFrontiers in bioengineering and biotechnology · 2026Article
- Effectiveness of local Tocilizumab administration in mitigating alveolar bone loss and inflammation in experimental periodontitis.Scientific reports · 2025Article
- Biomaterial-mediated macrophage polarization remodeling and sequential regulation: a potential strategy in bone infections treatment.Bone research · 2025Review
- The hidden driver of osteoporosis: mitochondria-dominated inflammation.Cell communication and signaling : CCS · 2025Review
- Article
- Exacerbating effects of Western dietary habits on experimentally induced periodontitis in rats.Odontology · 2025Article
- Exercise-Mediated Skeletal Muscle-Derived IL-6 Regulates Bone Metabolism: A New Perspective on Muscle-Bone Crosstalk.Biomolecules · 2025Review
- Expression and significance of cytokines in peripheral blood and bone microenvironment in Kummell's disease, osteoporotic vertebral compression fractures and nonosteoporotic patients.BMC musculoskeletal disorders · 2025Article
- Irisin alleviates obesity-induced bone loss by inhibiting interleukin 6 expression via TLR4/MyD88/NF-κB axis in adipocytes.Journal of advanced research · 2025Article
- SARS-CoV-2 Impairs Osteoblast Differentiation Through Spike Glycoprotein and Cytokine Dysregulation.Viruses · 2025Article
53 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It has been suggested that interleukin-6 (IL-6)plays a key role in the pathogenesis of rheumatoid arthritis(RA), including osteoporosis not only in inflamed joints but also in the whole body. However, previous in vitro studies regarding the effects of IL-6 on osteoblast differentiation are inconsistent. The aim of this study was to examine the effects and signal transduction of IL-6 on osteoblast differentiation in MC3T3-E1 cells and primary murine calvarial osteoblasts. IL-6 and its soluble receptor significantly reduced alkaline phosphatase (ALP) activity, the expression of osteoblastic genes (Runx2, osterix, and osteocalcin), and mineralization in a dose-dependent manner, which indicates negative effects of IL-6 on osteoblast differentiation. Signal transduction studies demonstrated that IL-6 activated not only two major signaling pathways, SHP2/MEK/ERK and JAK/STAT3, but also the SHP2/PI3K/Akt2 signaling pathway. The negative effect of IL-6 on osteoblast differentiation was restored by inhibition of MEK as well as PI3K, while it was enhanced by inhibition of STAT3. Knockdown of MEK2 and Akt2 transfected with siRNA enhanced ALP activity and gene expression of Runx2. These results indicate that IL-6 negatively regulates osteoblast differentiation through SHP2/MEK2/ERK and SHP2/PI3K/Akt2 pathways, while affecting it positively through JAK/STAT3. Inhibition of MEK2 and Akt2 signaling in osteoblasts might be of potential use in the treatment of osteoporosis in RA.
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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.