Hedderich, Jessica and El Bagdadi, Karima and Angele, Peter and Graessel, Susanne and Meurer, Andrea and Straub, Rainer H. and Zaucke, Frank and Jenei-Lanzl, Zsuzsa (2020) Norepinephrine Inhibits the Proliferation of Human Bone Marrow-Derived Mesenchymal Stem Cells via beta 2-Adrenoceptor-Mediated ERK1/2 and PKA Phosphorylation. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 21 (11): 3924. ISSN , 1422-0067
Full text not available from this repository. (Request a copy)Abstract
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 alpha 1-, alpha 2- or beta 1/2-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 (alpha 2B-, alpha 2C- and beta 2-AR) and OA BMSCs (alpha 2A-, alpha 2B-, and beta 2-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 beta 2-AR-mediated ERK1/2 and PKA phosphorylation. Therefore, targeting beta 2-AR-signaling might provide novel OA therapeutic options.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PROTEIN-KINASE PATHWAY; STROMAL CELLS; DNA-SYNTHESIS; EXPRESSION; ACTIVATION; CAMP; DIFFERENTIATION; CHONDROCYTES; STIMULATION; METABOLISM; bone marrow-derived mesenchymal stem cells (BMSCs); proliferation; regeneration; sympathicus; norepinephrine |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Unfallchirurgie Medicine > Lehrstuhl für Innere Medizin I Medicine > Lehrstuhl für Orthopädie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 22 Mar 2021 12:18 |
| Last Modified: | 22 Mar 2021 12:18 |
| URI: | https://pred.uni-regensburg.de/id/eprint/44460 |
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