Purpose
This review will discuss the role of vitamin D and calcium signaling in the epidermal wound response with particular focus on the stem cells of the epidermis and hair follicle that contribute ...to the wounding response.
Methods
Selected publications relevant to the mechanisms of wound healing in general and the roles of calcium and vitamin D in wound healing in particular were reviewed.
Results
Following wounding the stem cells of the hair follicle and interfollicular epidermis are activated to proliferate and migrate to the wound where they take on an epidermal fate to re-epithelialize the wound and regenerate the epidermis. The vitamin D and calcium sensing receptors (VDR and CaSR, respectively) are expressed in the stem cells of the hair follicle and epidermis where they play a critical role in enabling the stem cells to respond to wounding. Deletion of
Vdr
and/or
Casr
from these cells delays wound healing. The VDR is regulated by co-regulators such as the Med 1 complex and other transcription factors such as Ctnnb (beta-catenin) and p63. The formation of the Cdh1/Ctnn (E-cadherin/catenin) complex jointly stimulated by vitamin D and calcium plays a critical role in the activation, migration, and re-epithelialization processes.
Conclusion
Vitamin D and calcium signaling are critical for the ability of epidermal and hair follicle stem cells to respond to wounding. Vitamin D deficiency with the accompanying decrease in calcium signaling can result in delayed and/or chronic wounds, a major cause of morbidity, loss of productivity, and medical expense.
Abstract
The interest in vitamin D continues unabated with thousands of publications contributing to a vast and growing literature each year. It is widely recognized that the vitamin D receptor (VDR) ...and the enzymes that metabolize vitamin D are found in many cells, not just those involved with calcium and phosphate homeostasis. In this mini review I have focused primarily on recent studies that provide new insights into vitamin D metabolism, mechanisms of action, and clinical applications. In particular, I examine how mutations in vitamin D metabolizing enzymes—and new information on their regulation—links vitamin D metabolism into areas such as metabolism and diseases outside that of the musculoskeletal system. New information regarding the mechanisms governing the function of the VDR elucidates how this molecule can be so multifunctional in a cell-specific fashion. Clinically, the difficulty in determining vitamin D sufficiency for all groups is addressed, including a discussion of whether the standard measure of vitamin D sufficiency, total 25OHD (25 hydroxyvitamin) levels, may not be the best measure—at least by itself. Finally, several recent large clinical trials exploring the role of vitamin D supplementation in nonskeletal diseases are briefly reviewed, with an eye toward what questions they answered and what new questions they raised.
Vitamin D is not just for preventing rickets and osteomalacia. Recent findings in animal experiments, epidemiologic studies and clinical trials indicate that adequate vitamin D levels are important ...for cancer prevention, controlling hormone levels and regulating the immune response. Although 25 hydroxyvitamin D (25OHD) levels >10 ng/ml can prevent rickets and osteomalacia, these levels are not sufficient to provide these more recently discovered clinical benefits. Rather, levels of 25OHD >30 ng/ml are generally recommended. Determining optimal levels of 25OHD and the amount of vitamin D supplementation required to achieve those levels for the numerous actions of vitamin D will only be established with additional trials. In this review, these newer applications are summarized and therapeutic considerations are provided.
The First International Conference on Controversies in Vitamin D was held in Pisa, Italy, 14–16 June 2017. The meeting's purpose was to address controversies in vitamin D research, review the data ...available, to help resolve them, and suggest a research agenda to clarify areas of uncertainty. The serum 25‐hydroxyvitamin D 25(OH)D concentration i.e. the sum of 25(OH)D3 and 25(OH)D2 remains the critical measurement for defining vitamin D status. Assay variation for 25(OH)D has contributed to the current chaos surrounding efforts to define hypovitaminosis D. An essential requirement to develop a consensus on vitamin D status is that measurement of 25(OH)D and, in the future, other potential vitamin D biomarkers e.g. 1α,25(OH)2D3, 3‐epi‐25(OH)D, 24,25(OH)2D3, vitamin D‐binding protein, free/bioavailable 25(OH)D and parathyroid hormone be standardized/harmonized, to allow pooling of research data. Vitamin D Standardization Program tools are described and recommended for standardizing 25(OH)D measurement in research. In the future, similar methodology, based on National Institute for Standards and Technology standard reference materials, must be developed for other candidate markers of vitamin D status. Failure to standardize/harmonize vitamin D metabolite measurements is destined to promulgate continued chaos. At this time, 25(OH)D values below 12 ng ml–1 (30 nmol l–1) should be considered to be associated with an increased risk of rickets/osteomalacia, whereas 25(OH)D concentrations between 20 ng ml–1 and 50 ng ml–1 (50–125 nmol l–1) appear to be safe and sufficient in the general population for skeletal health. In an effort to bridge knowledge gaps in defining hypovitaminosis D, an international study on rickets as a multifactorial disease is proposed.
Abstract Skeletal muscle and bone rely on a number of growth factors to undergo development, modulate growth, and maintain physiological strength. A major player in these actions is insulin-like ...growth factor I (IGF-I). However, because this growth factor can directly enhance muscle mass and bone density, it alters the state of the musculoskeletal system indirectly through mechanical crosstalk between these two organ systems. Thus, there are clearly synergistic actions of IGF-I that extend beyond the direct activity through its receptor. This review will cover the production and signaling of IGF-I as it pertains to muscle and bone, the chemical and mechanical influences that arise from IGF-I activity, and the potential for therapeutic strategies based on IGF-I. This article is part of a Special Issue entitled “Muscle Bone Interactions”.
Significant controversy has emerged over the last decade concerning the effects of vitamin D on skeletal and nonskeletal tissues. The demonstration that the vitamin D receptor is expressed in ...virtually all cells of the body and the growing body of observational data supporting a relationship of serum 25-hydroxyvitamin D to chronic metabolic, cardiovascular, and neoplastic diseases have led to widespread utilization of vitamin D supplementation for the prevention and treatment of numerous disorders. In this paper, we review both the basic and clinical aspects of vitamin D in relation to nonskeletal organ systems. We begin by focusing on the molecular aspects of vitamin D, primarily by examining the structure and function of the vitamin D receptor. This is followed by a systematic review according to tissue type of the inherent biological plausibility, the strength of the observational data, and the levels of evidence that support or refute an association between vitamin D levels or supplementation and maternal/child health as well as various disease states. Although observational studies support a strong case for an association between vitamin D and musculoskeletal, cardiovascular, neoplastic, and metabolic disorders, there remains a paucity of large-scale and long-term randomized clinical trials. Thus, at this time, more studies are needed to definitively conclude that vitamin D can offer preventive and therapeutic benefits across a wide range of physiological states and chronic nonskeletal disorders.
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