International journal of molecular sciences, 2020-05, Vol.21 (11), p.3924
2020
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- Autor(en) / Beteiligte
- Titel
- Norepinephrine Inhibits the Proliferation of Human Bone Marrow-Derived Mesenchymal Stem Cells via β2-Adrenoceptor-Mediated ERK1/2 and PKA Phosphorylation
- Ist Teil von
- International journal of molecular sciences, 2020-05, Vol.21 (11), p.3924
- Ort / Verlag
- Switzerland: MDPI AG
- Erscheinungsjahr
- 2020
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Bone marrow-derived mesenchymal stem cells (BMSCs) represent an alternative to chondrocytes to support cartilage regeneration in osteoarthritis (OA). The sympathetic neurotransmitter norepinephrine (NE) has been shown to inhibit their chondrogenic potential; however, their proliferation capacity under NE influence has not been studied yet. Therefore, we used BMSCs obtained from trauma and OA donors and compared the expression of adrenergic receptors (AR). Then, BMSCs from both donor groups were treated with NE, as well as with combinations of NE and α1-, α2- or β1/2-AR antagonists (doxazosin, yohimbine or propranolol). Activation of AR-coupled signaling was investigated by analyzing ERK1/2 and protein kinase A (PKA) phosphorylation. A similar but not identical subset of ARs was expressed in trauma (α2B-, α2C- and β2-AR) and OA BMSCs (α2A-, α2B-, and β2-AR). NE in high concentrations inhibited the proliferation of both trauma and OA BMCSs significantly. NE in low concentrations did not influence proliferation. ERK1/2 as well as PKA were activated after NE treatment in both BMSC types. These effects were abolished only by propranolol. Our results demonstrate that NE inhibits the proliferation and accordingly lowers the regenerative capacity of human BMSCs likely via β2-AR-mediated ERK1/2 and PKA phosphorylation. Therefore, targeting β2-AR-signaling might provide novel OA therapeutic options.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1422-0067, 1661-6596eISSN: 1422-0067DOI: 10.3390/ijms21113924Titel-ID: cdi_doaj_primary_oai_doaj_org_article_24e0e26c7ac44581a2c5ef417352926a
- Format
- –
- Schlagworte
- Adrenergic receptors, Adult, Aged, Biomedical materials, Bone marrow, Bone Marrow Cells - cytology, bone marrow-derived mesenchymal stem cells (BMSCs), Cartilage, Cartilage diseases, Catecholamines, Cell proliferation, Cell Proliferation - drug effects, Cell Survival, Cells, Cultured, Chondrocytes, Chondrocytes - cytology, Cyclic AMP-Dependent Protein Kinases - metabolism, Doxazosin - pharmacology, Extracellular signal-regulated kinase, Extracellular Signal-Regulated MAP Kinases - metabolism, Female, Gene expression, Gene Expression Profiling, Humans, Influence, Kinases, Low concentrations, Male, MAP Kinase Signaling System - drug effects, Mesenchymal stem cells, Mesenchymal Stem Cells - cytology, Mesenchymal Stem Cells - drug effects, Middle Aged, Neurotransmitter Agents - metabolism, Neurotransmitters, Norepinephrine, Norepinephrine - pharmacology, Osteoarthritis, Phosphorylation, proliferation, Propranolol, Propranolol - pharmacology, Protein kinase A, Receptors (physiology), Receptors, Adrenergic, beta-2 - metabolism, Regeneration, Signal Transduction, Stem cells, Studies, sympathicus, Trauma, Yohimbine, Yohimbine - pharmacology, Young Adult