ArticleBoneKEy reports2015
Sclerostin inhibits osteoblast differentiation without affecting BMP2/SMAD1/5 or Wnt3a/β-catenin signaling but through activation of platelet-derived growth factor receptor signaling in vitro.
Article in BoneKEy reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Sclerostin blockade inhibits bone resorption through PDGF receptor signaling in osteoblast lineage cells.JCI insight · 2024Article
- Targeting strategies for bone diseases: signaling pathways and clinical studies.Signal transduction and targeted therapy · 2023Review
- Directed evolution identifies high-affinity cystine-knot peptide agonists and antagonists of Wnt/β-catenin signaling.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Modeling osteoporosis to design and optimize pharmacological therapies comprising multiple drug types.eLife · 2022Article
- The role of osteocytes-specific molecular mechanism in regulation of mechanotransduction - A systematic review.Journal of orthopaedic translation · 2021Review
- Reduction of mechanical loading in tendons induces heterotopic ossification and activation of the β-catenin signaling pathway.Journal of orthopaedic translation · 2021Article
- The Role of Sclerostin in Bone and Ectopic Calcification.International journal of molecular sciences · 2020Review
- Application of Cytokines of the Bone Morphogenetic Protein (BMP) Family in Spinal Fusion - Effects on the Bone, Intervertebral Disc and Mesenchymal Stromal Cells.Current stem cell research & therapy · 2019Review
- Article
- Review
- Effects of substrate stiffness and cell-cell contact on mesenchymal stem cell differentiation.Biomaterials · 2016Article
- MiR-9-5p, miR-675-5p and miR-138-5p Damages the Strontium and LRP5-Mediated Skeletal Cell Proliferation, Differentiation, and Adhesion.International journal of molecular sciences · 2016Article
- Copy number variations in 119 Chinese children with idiopathic short stature identified by the custom genome-wide microarray.Molecular cytogenetics · 2016Article
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Authors and funding
2 authors at 1 institution in 1 country.
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Abstract
Sclerostin inhibits bone formation mostly by antagonizing LRP5/6, thus inhibiting Wnt signaling. However, experiments with genetically modified mouse models suggest that a significant part of sclerostin-mediated inhibition of bone formation is due to interactions with other binding partners. The objective of the present work was to identify signaling pathways affected by sclerostin in relation with its inhibitory action on osteogenic differentiation of C3H10T1/2 cells, MC3T3-E1 cells and primary osteoblasts. Sclerostin inhibited BMP2-induced osteoblast differentiation without altering SMAD1/5 phosphorylation and transcriptional activity. Moreover, sclerostin prevented Wnt3a-mediated osteoblastogenesis without affecting LRP5/6 phosphorylation or β-catenin transcriptional activity. In addition, sclerostin inhibited mineralization promoted by GSK3 inhibition, which mimics canonical Wnt signaling without activation of LRP5/6, suggesting that sclerostin can prevent osteoblast differentiation without antagonizing LRP5/6. Finally, we found that sclerostin could activate platelet-derived growth factor receptor (PDGFR) and its downstream signaling pathways PLCγ, PKC, Akt and ERK1/2. PDGFR inhibition could reverse sclerostin-mediated inhibitory activity on BMP2-induced osteoblast differentiation. Therefore, our data suggest that sclerostin can activate PDGFR signaling by itself, and this functional interaction may be involved in the negative effect of sclerostin on osteoblast differentiation.
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Registered trials
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