Abstract
This Special Issue of Bioelectricity is concerned with the cells of load-bearing connective tissues in human physiology and pathophysiology. Alongside the highly specialized synovial joints, tendons, ligaments, and the intervertebral disk, we have more broadly considered cell types (e.g., adipocytes) that, to date, have unfortunately received less attention in a bioelectricity context. Even within the highly specialized functioning of these load-bearing cells, there is enormous diversity, which we are pleased to highlight here. With this initial collection, we welcomed the opportunity to draw attention of the scientific community to emerging cross-disciplinary research that connects ion channels to cell mechanics, signaling to growth, and makes use of mathematical modeling as well as innovative experimental techniques.
Thus, we cover original research, and reviews on mechanistic aspects of cellular signaling, electrophysiology, ion channels, exchangers, pumps, and macromolecular complexes. All these are involved in joint development, loading and pathophysiology. The latter includes degeneration, inflammation, immunometabolism, and immunosenescence.
The original research contribution of Smith et al. entitled “Intracellular Ca2+ in mouse white fat adipocytes: Effects of extracellular anions, growth hormone and their interaction with Ca2+ influx” probes the ubiquitous role of Ca2+ signaling in a new murine experimental model of adiposity. A very different approach is the study of Fischer et al.—“Probing the putative role of KATP channels and biological variability in a mathematical model of chondrocyte electrophysiology.” This employs mathematical modeling and simulation to investigate the resting membrane potential of the human articular chondrocyte more deeply. A full review article presented by Moatti et al.—“Enhancement of Bone Regeneration Through the Converse Piezoelectric Effect, A Novel Approach for Applying Mechanical Stimulation”—offers a thorough introduction to new hybrid methods for tissue regeneration. Finally, a perspective on “Mechanosensitive ion channels and stem cell differentiation” by Djamgoz and Pchelintseva rounds out this interdisciplinary collection.
The ambition level for this issue has been to offer insights into current cross-cutting studies and to inspire new submissions in this area. In future article collections focused on connective tissue cells, their tissues, and their bioelectric environments, we would be keen on including novel work on, for example, neoinnervation in osteoarthritis and linking growth factors (e.g., nerve growth factor) to nociception. Such pathological processes and bioelectric links to mechanisms of nociception/pain imply neuroscience solutions for arthritis.
We view this special issue as a “jumpstart” and a work in progress. A great deal more work needs to be done to highlight emerging interdisciplinary work and opportunities therein. We would like to promote a “holistic” view of bioelectricity in connective tissue cells, integrating environmental factors (physiological parameters, endocrine agents, biological molecules, and signaling pathways involved in joint development and degeneration). This could readily lead to further application-based work, for example, drug design and regenerative tissue studies, among others. Such studies hold enormous relevance for the fields of joint development and maintenance, and aging and pathophysiology, including degeneration, inflammation, and immunometabolism.
One can look forward to this field's future development. Indeed, already in focus for many is joining core research in connective tissue physiology together with the bioelectricity of cell regeneration. We believe that hybrid and emerging methods including mathematical modeling, data science, and machine learning, as well as advances in animal models and imaging, will be instrumental in moving forward.
It would be remiss to not recognize Prof. David Julius (University of California, San Francisco) and Prof. Ardem Patapoutian (Howard Hughes Medical Institute, Scripps Research, La Jolla, CA) on winning the 2021 Nobel Prize for physiology or medicine for their discovery of transient receptor potential and piezo channels (highlighted in relation to stem cell differentiation in the perspective of Djamgoz and Pchelintseva). These seminal studies uncovered the bioelectric and molecular basis of our ability to feel, interpret, and interact with our internal and external environments. Clearly, a great deal of work needs to be done to facilitate the translation of the research into new and innovative drugs for treating diseases with unmet medical needs. This is a challenge that will require cross-disciplinary collaboration.
Finally, as guest editors, we would like to call the readers' attention to a future special section—in the March 2022 issue—with additional articles focused on the bioelectricity of connective tissue cells and their environments. A particular highlight will be the “My Experiments in Bioelectricity” article by Alan Grodzinsky (professor of electrical, mechanical and biological engineering and director of the Center for Biomedical Engineering at MIT).