ArticleBMC musculoskeletal disorders2019
Transforming growth factor-β stimulates nerve growth factor production in osteoarthritic synovium.
Article in BMC musculoskeletal disorders, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Photobiomodulation Therapy Modulates Inflammatory and Cartilage Biomarkers in Patients with Knee Osteoarthritis: A Pilot Case Series.Journal of orthopaedic case reports · 2026Article
- Mechanistic insights into cartilage-sensory nerve crosstalk in osteoarthritis progression.Journal of orthopaedic translation · 2026Review
- Understanding pain heterogeneity in osteoarthritis patients: a narrative review.Frontiers of medicine · 2025Review
- Distinct late-stage osteoarthritis profiles identified through NF-κB, TNF-α, and TGF-β-driven synovial inflammation and pain.Scientific reports · 2025Article
- Inhibitory effect of MLC901 on axonal demyelination in experimental animals undergoing circumferential lumbal stenosis by increasing transforming growth factor-β1 levels.Asian spine journal · 2025Article
- Effect of ELHLD peptide for stifle function recovery after tibial plateau leveling osteotomy in dogs.Journal of veterinary science · 2025Article
- Silencing miR-21-5p in sensory neurons reverses neuropathic allodynia via activation of TGF-β-related pathway in macrophages.The Journal of clinical investigation · 2023Article
- Insights into osteoarthritis development from single-cell RNA sequencing of subchondral bone.RMD open · 2022Article
- Genome-Wide RNA Sequencing of Human Trabecular Meshwork Cells Treated with TGF-β1: Relevance to Pseudoexfoliation Glaucoma.Biomolecules · 2022Article
- Synovial inflammation in osteoarthritis progression.Nature reviews. Rheumatology · 2022Review
- Increased serum AXL is associated with radiographic knee osteoarthritis severity.International journal of rheumatic diseases · 2022Article
- Characteristics of sensory innervation in synovium of rats within different knee osteoarthritis models and the correlation between synovial fibrosis and hyperalgesia.Journal of advanced research · 2022Article
- TGF-β regulates nerve growth factor expression in a mouse intervertebral disc injury model.BMC musculoskeletal disorders · 2021Article
- Article
- Regeneration of Damaged Tendon-Bone Junctions (Entheses)-TAK1 as a Potential Node Factor.International journal of molecular sciences · 2020Review
- Plasma MMP-9, TIMP-1, and TGF-β1 Responses to Exercise-Induced Muscle Injury.International journal of environmental research and public health · 2020Article
- Increased nerve growth factor expression in the synovial tissues of patients with rotator cuff tears.Molecular painArticle
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundNerve growth factor (NGF) contributes to pain in knee osteoarthritis (KOA) patients. Transforming growth factor-beta (TGF-β) stimulates NGF expression in chondrocytes from KOA patients. However, the correlation between synovial TGF-β and NGF levels has not been sufficiently studied in human KOA patients. Further, the mechanism governing NGF regulation by TGF-β in synovial cells is unclear.
methodsDuring total knee arthroplasty, we extracted the synovial tissue (SYT) of 107 subjects with unilateral Kellgren/Lawrence grade 3-4 KOA confirmed by radiography. We examined the distribution of TGF-β and NGF using immunohistochemistry, and analyzed the relationship between NGF and TGFB mRNA levels. Cultured synovial cells extracted from SYT were exposed to culture medium (control), human recombinant TGF-β (rhTGF-β), rhTGF-β + ALK5 inhibitor SB505124, rhTGF-β + transforming growth factor activating kinase 1 (TAK1) inhibitor (5Z)-7-oxozeaenol, or rhTGF-β + p38 inhibitor SB203580 for 30 min, 6 h and 24 h. NGF mRNA expressed by the cultured cells and NGF protein levels in the cell supernatant were detected by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Phosphorylation of p38 was evaluated by western blotting.
resultsNGF mRNA levels were positively correlated with those of TGFB. Cells expressing TGF-β and NGF protein were observed in the lining layer of SYT. TGF-β stimulated increased NGF mRNA expression and NGF protein production. The ALK5 inhibitor completely suppressed the TGF-β-mediated increase in NGF expression and NGF production in synovial cells. ALK5, TAK1 and p38 inhibitors inhibited the TGF-β-induced phosphorylation of p38, and TAK1 and p38 inhibitors partially inhibited the TGF-β-mediated increase in NGF expression and NGF production in synovial cells.
conclusionTGF-β regulates NGF production via the TGF-β/ALK5 signaling pathway in osteoarthritic synovium. This effect may partially occur through inhibition of the TAK1/p38 pathway in the SYT of KOA patients.
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