Cell death & disease, 2019-04, Vol.10 (5), p.350-350, Article 350
2019
Details
- Autor(en) / Beteiligte
- Titel
- Enhanced osteogenic differentiation of mesenchymal stem cells in ankylosing spondylitis: a study based on a three-dimensional biomimetic environment
- Ist Teil von
- Cell death & disease, 2019-04, Vol.10 (5), p.350-350, Article 350
- Ort / Verlag
- England: Springer Nature B.V
- Erscheinungsjahr
- 2019
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- The mechanism of pathological osteogenesis in Ankylosing spondylitis (AS) is largely unknown. Our previous studies demonstrated that the imbalance between BMP-2 and Noggin secretion induces abnormal osteogenic differentiation of marrow-derived mesenchymal stem cells (MSCs) from AS patients in a two-dimensional culture environment. In this study, HA/β-TCP scaffolds were further used as a three-dimensional (3D) biomimetic culture system to mimic the bone microenvironment in vivo to determine the abnormal osteogenic differentiation of AS-MSCs. We demonstrated that when cultured in HA/β-TCP scaffolds, AS-MSCs had a stronger osteogenic differentiation capacity than that of MSCs from healthy donors (HD-MSCs) in vitro and in vivo. This dysfunction resulted from BMP2 overexpression in AS-MSCs, which excessively activated the Smad1/5/8 and ERK signalling pathways and finally led to enhanced osteogenic differentiation. Both the signalling pathway inhibitors and siRNAs inhibiting BMP2 expression could rectify the enhanced osteogenic differentiation of AS-MSCs. Furthermore, BMP2 expression in ossifying entheses was significantly higher in AS patients. In summary, our study demonstrated that AS-MSCs possess enhanced osteogenic differentiation in HA/β-TCP scaffolds as a 3D biomimetic microenvironment because of BMP2 overexpression, but not Noggin. These results provide insights into the mechanism of pathological osteogenesis, which can aid in the development of niche-targeting medications for AS.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-4889eISSN: 2041-4889DOI: 10.1038/s41419-019-1586-1Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6484086
- Format
- –
- Schlagworte
- Ankylosing spondylitis, Biomimetic Materials - chemistry, Bone morphogenetic protein 2, Bone Morphogenetic Protein 2 - antagonists & inhibitors, Bone Morphogenetic Protein 2 - genetics, Bone Morphogenetic Protein 2 - metabolism, Calcium Phosphates - chemistry, Cell culture, Cell Differentiation, Cell Proliferation, Cells, Cultured, Culture Techniques - methods, Durapatite - chemistry, Extracellular Signal-Regulated MAP Kinases - metabolism, Humans, Mesenchymal stem cells, Mesenchymal Stem Cells - cytology, Mesenchymal Stem Cells - metabolism, Mesenchyme, Noggin protein, Osteogenesis, RNA Interference, RNA, Small Interfering - metabolism, Secretion, Signal Transduction, siRNA, Smad1 Protein - metabolism, Smad5 Protein - metabolism, Smad8 Protein - metabolism, Spondylitis, Spondylitis, Ankylosing - metabolism, Spondylitis, Ankylosing - pathology, Stem cells, Tissue Scaffolds - chemistry