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Norepinephrine Inhibits Synovial Adipose Stem Cell Chondrogenesis via α2a-Adrenoceptor-Mediated ERK1/2 Activation

1
Dr. Rolf M. Schwiete Research Unit for Osteoarthritis, Orthopedic University Hospital Friedrichsheim gGmbH, 60528 Frankfurt/Main, Germany
2
Laboratory of Experimental Rheumatology and Neuroendocrine Immunology, Department of Internal Medicine, University Hospital Regensburg, 93053 Regensburg, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(13), 3127; https://doi.org/10.3390/ijms20133127
Received: 21 May 2019 / Revised: 25 June 2019 / Accepted: 25 June 2019 / Published: 26 June 2019
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Abstract

In recent years, first evidences emerged that sympathetic neurotransmitters influence osteoarthritis (OA) manifestation. Joint-resident stem cells might contribute to cartilage repair, however, their chondrogenic function is reduced. The neurotransmitter norepinephrine (NE) was detected in the synovial fluid of trauma and OA patients. Therefore, the aim of this study was to analyse how NE influences the chondrogenesis of synovial adipose tissue-derived stem cells (sASCs). sASCs were isolated from knee-OA patients synovia. After adrenoceptor (AR) expression analysis, proliferation and chondrogenic differentiation in presence of NE and/or α- and β-AR antagonist were investigated. Cell count, viability, chondrogenic and hypertophic gene expression, sulfated glycosaminoglycan (sGAG) and type II collagen content were determined. Key AR-dependent signaling (ERK1/2, PKA) was analyzed via western blot. sASC expressed α1A-, α1B-, α2A-, α2B-, α2C-, and β2-AR in monolayer and pellet culture. NE did not affect proliferation and viability, but 10−7 and 10−6 M NE significantly reduced sGAG and type II collagen content as well as ERK1/2 phosphorylation. These effects were fully reversed by yohimbine (α2-AR antagonist). Our study confirms the important role of NE in sASC chondrogenic function and provides new insights in OA pathophysiology. Future studies might help to develop novel therapeutic options targeting neuroendocrine pathways for OA treatment. View Full-Text
Keywords: synovial adipose stem cells; sympathicus; norepinephrine; adrenoceptors; chondrogenesis; osteoarthritis; physioxia synovial adipose stem cells; sympathicus; norepinephrine; adrenoceptors; chondrogenesis; osteoarthritis; physioxia
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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El Bagdadi, K.; Zaucke, F.; Meurer, A.; Straub, R.H.; Jenei-Lanzl, Z. Norepinephrine Inhibits Synovial Adipose Stem Cell Chondrogenesis via α2a-Adrenoceptor-Mediated ERK1/2 Activation. Int. J. Mol. Sci. 2019, 20, 3127.

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