Hecht, N. and Johnstone, B. and Angele, P. and Walker, T. and Richter, W. (2019) Mechanosensitive MiRs regulated by anabolic and catabolic loading of human cartilage. OSTEOARTHRITIS AND CARTILAGE, 27 (8). pp. 1208-1218. ISSN 1063-4584, 1522-9653
Full text not available from this repository. (Request a copy)Abstract
Objective: Elucidation of whether miRs are involved in mechanotransduction pathways by which cartilage is maintained or disturbed has a particular importance in our understanding of osteoarthritis (OA) pathophysiology. The aim was to investigate whether mechanical loading influences global miR-expression in human chondrocytes and to identify mechanosensitive miRs responding to beneficial and non-beneficial loading regimes as potential to obtain valuable diagnostic or therapeutic targets to advance OA-treatment. Method: Mature tissue-engineered human cartilage was subjected to two distinct loading regimes either stimulating or suppressing proteoglycan-synthesis, before global miR microarray analysis. Promising candidate miRs were selected, re-evaluated by qRT-PCR and tested for expression in human healthy vs OA cartilage samples. Results: After anabolic loading, miR microarray profiling revealed minor changes in miR-expression while catabolic stimulation produced a significant regulation of 80 miRs with a clear separation of control and compressed samples by hierarchical clustering. Cross-testing of selected miRs revealed that miR-221, miR-6872-3p, miR-6723-5p were upregulated by both loading conditions while others (miR-199b-5p, miR-1229-5p, miR-1275, miR-4459, miR-6891-5p, miR-7150) responded specifically after catabolic loading. Mechanosensitivity of miR-221 correlated with pERK1/2-activation induced by both loading conditions. The miR-response to loading was transient and a constitutive deregulation of mechano-miRs in OA vs healthy articular cartilage was not observed. Conclusions: MiRs with broader vs narrower mechanosensitivity were discovered and the first group of mechanosensitive miRs characteristic for non-beneficial loading was defined that may shape the proteome differentially when cartilage tissue is disturbed. The findings prompt future investigations into miR-relevance for mechano-responsive pathways and the corresponding miR-target molecules. (C) 2019 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HUMAN OSTEOARTHRITIC CARTILAGE; ARTICULAR-CARTILAGE; COLLAGEN-SYNTHESIS; STEM-CELLS; MICRORNA; EXPRESSION; TARGETS; RNA; DIFFERENTIATION; PROLIFERATION; Mechanical loading; miR-profiling; Engineered cartilage; Osteoarthritis |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Unfallchirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 01 Apr 2020 08:57 |
| Last Modified: | 01 Apr 2020 08:57 |
| URI: | https://pred.uni-regensburg.de/id/eprint/26569 |
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