TY - JOUR
T1 - Mechanosensitive MiRs regulated by anabolic and catabolic loading of human cartilage
AU - Hecht, N.
AU - Johnstone, B.
AU - Angele, P.
AU - Walker, T.
AU - Richter, W.
N1 - Funding Information:
This study was supported by the German Research Foundation DFG -grant RI707/12-1 as part of the Excarbon Research Group FOR2407 .
Funding Information:
We thank Nina Hofmann and Melanie Weisser for excellent technical assistance and Simone Gantz for professional statistical advice. Special thanks to Jessica Gabler for the help in microRNA data evaluation and interpretation. We thank the RMS Foundation for providing the β-TCP constructs and I. Heschel from Matricel for donation of the Optimaix scaffolds. We thank the microarray unit of the DKFZ Genomics and Proteomics Core Facility for providing the Agilent miRNA Microarray and related services. This study was supported by the German Research Foundation DFG-grant RI707/12-1 as part of the Excarbon Research Group FOR2407.
Funding Information:
This study was supported by the German Research Foundation DFG-grant RI707/12-1 as part of the Excarbon Research Group FOR2407. We thank Nina Hofmann and Melanie Weisser for excellent technical assistance and Simone Gantz for professional statistical advice. Special thanks to Jessica Gabler for the help in microRNA data evaluation and interpretation. We thank the RMS Foundation for providing the ?-TCP constructs and I. Heschel from Matricel for donation of the Optimaix scaffolds. We thank the microarray unit of the DKFZ Genomics and Proteomics Core Facility for providing the Agilent miRNA Microarray and related services. This study was supported by the German Research Foundation DFG-grant RI707/12-1 as part of the Excarbon Research Group FOR2407.
Funding Information:
This study was supported by the German Research Foundation DFG-grant RI707/12-1 as part of the Excarbon Research Group FOR2407.
Publisher Copyright:
© 2019 Osteoarthritis Research Society International
PY - 2019/8
Y1 - 2019/8
N2 - 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.
AB - 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.
KW - Engineered cartilage
KW - Mechanical loading
KW - Osteoarthritis
KW - miR-profiling
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U2 - 10.1016/j.joca.2019.04.010
DO - 10.1016/j.joca.2019.04.010
M3 - Article
C2 - 31009748
AN - SCOPUS:85065215444
SN - 1063-4584
VL - 27
SP - 1208
EP - 1218
JO - Osteoarthritis and Cartilage
JF - Osteoarthritis and Cartilage
IS - 8
ER -