El Bagdadi, Karima and Zaucke, Frank and Meurer, Andrea and Straub, Rainer H. and Benitez-Paez, Zsuzsa (2019) Norepinephrine Inhibits Synovial Adipose Stem Cell Chondrogenesis via alpha 2a-Adrenoceptor-Mediated ERK1/2 Activation. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 20 (13): 3127. ISSN 1422-0067,
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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 alpha- and beta-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 alpha 1A-, alpha 1B-, alpha 2A-, alpha 2B-, alpha 2C-, and beta 2-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 (alpha 2-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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MESENCHYMAL STROMAL CELLS; SYMPATHETIC-NERVE FIBERS; ARTICULAR-CARTILAGE; CHONDROCYTE; RECEPTOR; OSTEOARTHRITIS; EXPRESSION; TISSUE; STIMULATION; ARTHRITIS; synovial adipose stem cells; sympathicus; norepinephrine; adrenoceptors; chondrogenesis; osteoarthritis; physioxia |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 03 Apr 2020 12:39 |
| Last Modified: | 03 Apr 2020 12:39 |
| URI: | https://pred.uni-regensburg.de/id/eprint/26724 |
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