| Item type: | Article | ||||
|---|---|---|---|---|---|
| Journal or Publication Title: | Osteoarthritis and Cartilage | ||||
| Publisher: | Elsevier | ||||
| Place of Publication: | OXFORD | ||||
| Volume: | 27 | ||||
| Number of Issue or Book Chapter: | 8 | ||||
| Page Range: | pp. 1208-1218 | ||||
| Date: | 2019 | ||||
| Institutions: | Medicine > Lehrstuhl für Unfallchirurgie | ||||
| Identification Number: |
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| Keywords: | HUMAN OSTEOARTHRITIC CARTILAGE; ARTICULAR-CARTILAGE; COLLAGEN-SYNTHESIS; STEM-CELLS; MICRORNA; EXPRESSION; TARGETS; RNA; DIFFERENTIATION; PROLIFERATION; Mechanical loading; miR-profiling; Engineered cartilage; Osteoarthritis | ||||
| Dewey Decimal Classification: | 600 Technology > 610 Medical sciences Medicine | ||||
| Status: | Published | ||||
| Refereed: | Yes, this version has been refereed | ||||
| Created at the University of Regensburg: | Yes | ||||
| Item ID: | 48425 |
Web of ScienceAbstract
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 ...
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.
Metadata last modified: 03 Sep 2021 09:55
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