About this Research Topic
Widely involved in cell signalling, either by direct signal transduction or acting as a second messenger, calcium (Ca2+) regulates a large range of physiological cell functions and processes including regulatory effects on many enzymes and proteins, muscle contraction, neuronal transmission and genesis, cellular motility and growth and. Ca2+, together with phosphate (P), also participates in the mineralization of calcified tissues where bones act as Ca2+storage site, intimately linked with the preservation of Ca2+ balance within the non-bone tissues of the body.
In order to maintain Ca2+ at a constant level, cells have developed a complex machinery. The regulation of Ca2+ homeostasis involves two major hormones, the parathyroid hormone (PTH), secreted by the parathyroid glands, and the active form of the vitamin D (1,25-dihydroxyvitaminD3), produced by the proximal tubular cells in the kidney. The regulation of PTH secretion in response to serum Ca2+ variation is monitored by the Ca2+ sensing receptor (CaSR). Although PTH secretion and action has been long known, the activity of the CaSR was characterized recently. Additionally, the role of FGF23 (a molecule associated with P metabolism) in Ca2+ homeostasis, remains limited.
In the skeleton, Ca2+ and P metabolism work in concert with osteoblasts, osteocytes, and extracellular matrix proteins involved in progressively organizing and ultimately mineralizing the osteoid matrix. In non-skeletal tissues, the regulatory system that prevents the harmful deposition of ectopic Ca2+-P complexes in soft tissues is less understood.
Recent research has focused on understanding the intracellular, transcellular and paracellular pathways of Ca2+ transport. Because mutations in some of the components of intracellular Ca2+ influx (e.g., ORAI1, STIM1) are associated with distinct disease syndromes, a better understanding of the mechanisms through which Ca2+ uptake occurs in cells is essential.
Additionally, tight junction proteins called claudins, which regulate the permeability of the epithelium by creating either pores or barriers to ions and other small molecules, have an emerging role in Ca2+ balance and mineralization. Mutations in claudins (e.g., Claudin-16/19, -18) affect several organs including kidneys, teeth, and bone, leading to the formation of kidney stones, amelogenesis imperfecta, and osteoporosis.
Despite recent advances, current research continues to address the regulation of Ca2+ homeostasis including: i) mechanisms of intracellular Ca2+ influx; ii) the role of CaSR and FGF23 in Ca2+ homeostasis and mineralization; iii) the expression profile of claudins in different tissues, their physiological function, and interaction with other regulators of Ca2+ homeostasis; iv) regulatory system preventing the deposition of ectopic Ca2+-P complexes in soft tissue; v) a clinical spectrum, diagnostic and therapeutic approach to the patients carrying the mutations in genes responsible for Ca2+ signalling and transport.
In order to address the gaps in knowledge described above, a multidisciplinary team from different countries, including both basic and clinical scientists (endocrinologists, nephrologists, gastroenterologists, and dentists) with expertise in the field of Ca2+ homeostasis, will contribute to the development of a Research Topic in “Frontiers in Endocrinology”, trying to have a 360-degree view in Ca2+ field and covering the following themes:
• Ca2+ influx: physiological aspects of Ca2+ uptake and extrusion, Ca2+ signaling in the endoplasmic reticulum and mitochondria
• Ca2+ influx: from physiological mechanisms to channelopathy (clinical phenotype, diagnostic and therapeutic approach to patients presenting with mutations)
• Ca2+ and hormone signalling: the role of FGF23 and CaSR
• Ca2+ and claudins: physiological aspects of expression, function, and interaction with other regulators, and pathologic conditions
• Ca2+ deposition and biomineralization proteins
• Ectopic Ca2+-P deposition in soft tissues: from physiological regulating mechanisms to pathophysiology
The types of manuscripts considered for the Research Topic:
- Original articles (clinical and basic)
- Reviews and mini-reviews
- Clinical cases
Keywords: calcium transport and signalling, claudins, FGF23, ectopic mineralization, impaired amelogenesis, nephrolitiasis, osteoporosi
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.