Abstract
Degeneration is a hallmark of autoimmune diseases, whose incidence grows worldwide. Current therapies attempt to control the immune response to limit degeneration, commonly promoting immunodepression. Differently, mechanical stimulation is known to trigger healing (regeneration) and it has recently been proposed locally for its therapeutic potential on severely injured areas. As the early stages of healing consist of altered intra- and inter-cellular fluxes of soluble molecules, we explored the potential of this early signal to spread, over time, beyond the stimulation district and become systemic, to impact on distributed or otherwise unreachable injured areas. We report in a model of arthritis in rats how stimulations delivered in the subcutaneous dorsal tissue result, over time, in the control and healing of the degeneration of the paws’ joints, concomitantly with the systemic activation of wound healing phenomena in blood and in correlation with a more eubiotic microbiome in the gut intestinal district.
Highlights
Mechanosensing is a pervasive ability of living cells, the informed exploitation of this characteristic is still in its infancy
We here present the results of this investigation tested on a model of rheumatoid arthritis (Collagen Induced Arthritis, CIA6) induced in animals (Wistar rats)
The study includes untreated healthy animals (NOCIA) and CIA animals cured with: methotrexate (MTX, gold standard7), mechanical stimulation (MS, subcutaneous dorsal stimulation), placebo for MTX (PLA, sterile saline solution (0.9% NaCl)) and control inhalational anesthetic (ANE, isoflurane, versus ether used in PLA, MS and MTX during animals’ blood sampling)
Summary
The flow of information that we here describe permits to read the control on CIA symptoms as the different effects of the multifaceted phenomenon of epithelial mesenchymal transition type[2], investing the district associated to the mild therapeutic injury (needle insertion and rotation), but spreading to the whole organism, via small signaling molecules, typical of early healing and mechanotransduction, conditioning the biochemical signaling in blood in continuous crosstalk with the GI microbiome, and globally defusing the inflammatory environment typical of the disease This promotes a virtuous control on the immune response, body-wise, and as a consequence in the special district target of the disease: the joints synovium, leading to a traceable reduction of a specific systemic arthritis biomarker like ADORA3. Translation in humans and further characterization of the phenomenon may find broad applicability in evidence based medicine for the treatment of autoimmune and degenerative diseases
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