Nuclear Magnetic Resonance Therapy Modulates the miRNA Profile in Human Primary OA Chondrocytes and Antagonizes Inflammation in Tc28/2a Cells.

Bibiane Steinecker-Frohnwieser,Nicole Eck,Werner Kullich,Anda Mann,Birgit Lohberger,Andreas Leithner,Lukas Weigl,Cornelia Kratschmann

doi:10.3390/ijms22115959

Abstract

Nuclear magnetic resonance therapy (NMRT) is discussed as a participant in repair processes regarding cartilage and as an influence in pain signaling. To substantiate the application of NMRT, the underlying mechanisms at the cellular level were studied. In this study microRNA (miR) was extracted from human primary healthy and osteoarthritis (OA) chondrocytes after NMR treatment and was sequenced by the Ion PI Hi-Q™ Sequencing 200 system. In addition, T/C-28a2 chondrocytes grown under hypoxic conditions were studied for IL-1β induced changes in expression on RNA and protein level. HDAC activity an NAD(+)/NADH was measured by luminescence detection. In OA chondrocytes miR-106a, miR-27a, miR-34b, miR-365a and miR-424 were downregulated. This downregulation was reversed by NMRT. miR-365a-5p is known to directly target HDAC and NF-ĸB, and a decrease in HDAC activity by NMRT was detected. NAD+/NADH was reduced by NMR treatment in OA chondrocytes. Under hypoxic conditions NMRT changed the expression profile of HIF1, HIF2, IGF2, MMP3, MMP13, and RUNX1. We conclude that NMRT changes the miR profile and modulates the HDAC and the NAD(+)/NADH signaling in human chondrocytes. These findings underline once more that NMRT counteracts IL-1β induced changes by reducing catabolic effects, thereby decreasing inflammatory mechanisms under OA by changing NF-ĸB signaling.

Highlights

Osteoarthritis (OA) represents the most common form of degenerative joint disease and is characterized by alterations of the cartilage extracellular matrix composition
We further investigated whether the treatment of OA chondrocytes with nuclear magnetic resonance therapy (NMRT) can counteract this OA induced miR
The log2 fold change analysis of the NMRT effect on OA cells when compared to healthy chondrocytes (HC) cells resulted in slight differences represented by the heat map (Figure S1B)

Summary

Introduction

Osteoarthritis (OA) represents the most common form of degenerative joint disease and is characterized by alterations of the cartilage extracellular matrix composition. The underlying degradation of the articular cartilage associated with the limited repair capacity leads to joint integrity disruption and progressive irreversible dysfunction [1]. Therapeutic agent concepts coupled with surgical techniques have been developed to treat patients with OA, there are no real effective medical therapies to prevent cartilage destruction and the associated changes in joints and bone. There is an attempt to use therapeutic nuclear magnetic resonance therapy (NMRT) in OA treatment. In clinical observations NMRT has been demonstrated to cause positive effects when applied to treat painful disorders of the musculoskeletal system [2]. While less was known about NMRT and its function at the cellular level [5], our previous work depicts positive effects of NMRT on the subthreshold

Results

Discussion

Conclusion