The MBST therapy or “MultiBioSignalTherapie” was developed in Germany in the 1990s as a derivative of the Magnetic Resonance Imaging (MRI) technology. Similar to MRI, the MBST system is based on the physical principle of nuclear magnetic resonance (NMR) and was originally designed to treat patients suffering from musculoskeletal diseases such as osteoarthritis (OA) or osteoporosis. Until today, the molecular effects of NMR on biological systems such as cells and organisms are poorly understood. In this context, the circadian clock and the hypoxic signaling pathway have been repeatedly shown to be mutually intertwined and known to play a crucial role in the maintenance of physiological homeostasis in cartilage as well as in the development and progression of OA.
The present study investigates the impact of NMR on the mRNA oscillation of circadian core clock genes, cryptochrome1, period1, period2, and clock1 and of Hypoxia Inducible Factor (Hif) isoforms, Hif-1, Hif-2, and Hif-3. To this end, zebrafish larvae aged 10 days post-fertilization (dpf) were treated with NMR for 1 hour on 4 consecutive days (from 11 to 14 dpf) at constant dim light conditions of 3 Lux. By using real-time qPCR the circadian mRNA oscillations were quantified. Finally, in order to test the presence of circadian rhythms, a cosinor analysis was performed, in which the data were fit to two alternative regression models: a straight-line as null hypothesis and a circadian damped cosine curve as alternative hypothesis.
The comparison of the results of the control (sham) animals with those of the NMR treated ones revealed that circadian oscillations of cryptochrome1 and period1 were restored in NMR treated zebrafish larvae, while those of period2 and clock1 remained unaffected. Furthermore, NMR also restored the circadian expression of Hif-1 and Hif-3, but did not show any effect in the temporal expression profile of Hif-2.
In summary, it can be concluded that NMR on a transcriptional level in zebrafish larvae affects both, the circadian clock and the hypoxic signaling pathway. In particular, the results indicate that NMR specifically affects the clock genes cry1 and per1, and, targets only circadian regulated Hif isoforms and thus, the hypoxic signaling pathway only indirectly.