Windmill, J. F. | bioRxiv Science

bioRxiv2025

Nanovibrational stimulation of osteogenesis engages non-canonical Wnt signalling and NF-κB regulator BCL3 as a mechanotransducer

Enhancing osteogenesis in mesenchymal stromal (stem) cells is essential for advancing cellular therapies that target and alleviate skeletal pathologies. By employing a bespoke bioreactor capable of delivering nano-amplitude vibration (30 nm, 1kHz) to human adipose-derived mesenchymal stromal cells, we observed osteo-specific differentiation. We related this to the mechanotransductive mechanism by showing that inhibition of intracellular tension results in the loss of cytoskeletal organisation and myosin activation driven by nanovibration. Further, we dissect the mechanism of osteogenesis using a panel of Wnt agonists and antagonists and highlight the role of non-canonical Wnt. Then, using Bcl3-/- cells and by stimulating with BCL3 peptide, we show that non-canonical Wnt, osteogenesis-related inflammation and osteogenesis itself are all regulated by BCL3. This is important as nanoscale direct cell-stimulation is gaining interest, and there is an emerging consensus that such signals can be osteogenic. While prior research has only broadly hinted at how nanovibrational signals convert to an osteogenic phenotype, this new work pinpoints critical mechanistic insights, thereby advancing our understanding of this promising avenue in musculoskeletal cell therapy.

bioengineering↗

bioRxiv2019

Physiological Basis of noise-induced hearing loss in a tympanal ear

Acoustic overexposure, such as listening to music too loud and too often, results in noise-induced hearing loss. The pathologies of this prevalent sensory disorder begin in the synapses of the primary auditory receptors, their postsynaptic partners and supporting cells. The extent of noise-induced damage, however, is determined by over-stimulation of primary auditory receptors. When over-stimulated, an excessive amount of positive ions flood into the primary auditory receptors, triggering the activation of ion channels and possibly disrupting their ability to encode sound. A systematic characterisation of the electrophysiological function of primary auditory receptors is warranted to understand how noise-exposure impacts on downstream targets, where the pathologies of hearing loss begin. Here, we used the experimentally-accessible locust ear to characterise noise-induced changes in the auditory receptors. Although, we found a decrease in ability of the primary auditory neurons to encode sound, this is probably due to pathologies of their supporting cells.

neuroscience↗