Current Opinion in Endocrine and Metabolic Research最新文献

Osteoblasts are the chief bone-making cells that specialize in producing and mineralizing large amounts of type I collagen and other matrix proteins. The bioenergetics in support of the energy-intensive osteoblast activity is not well understood but has gained renewed interest in recent years. Research in the past ten years has not only confirmed glucose as the main energy substrate for osteoblasts, but also identified contributions of amino acids and fatty acids to either bioenergetic or biosynthetic processes in the cell. Moreover, osteogenic signals have been functionally linked to substrate utilization in osteoblasts. The brief review aims to summarize the recent findings, and to identify remaining questions in the emerging field.

Recent advancements in the bone biology field have identified a novel bone-metabolism axis. In this review, we highlight several novel studies that further our knowledge of new endocrine functions of bone; explore remaining unanswered questions; and discuss translational challenges in this complex era of bone biology research.

The hypoxia-inducible factor 2alpha (HIF-2), which is a member of the HIF family of transcription factors and a critical component of the hypoxia-driven pathway, regulates adult erythropoiesis through the renal production and secretion of erythropoietin (EPO). Notably, circulating EPO also affects bone mass through either direct or indirect actions on osteoblastic and osteoclastic cells. Adding complexity to the picture, we have recently reported that osteoblastic cells produce and secrete EPO upon activation of HIF-2. Although physiological role of osteoblastic EPO in controlling hematopoiesis remains to be determined, our findings could have translational implications for the treatment of anemia.

FGF23 is essential for the regulation of serum phosphate level and the aberrant actions of FGF23 cause hypophosphatemic or hyperphosphatemic diseases. The objective of this review is to provide a current and relevant summary of the recent basic and clinical findings concerning FGF23. Recent findings: Many factors have been shown to affect FGF23 production while the precise roles of these factors in phosphate metabolism are largely unknown. Anti-FGF23 antibody has become clinically available, and the efficacy of this antibody has been reported in several hypophosphatemic diseases caused by excessive actions of FGF23.Summary: The identification of FGF23 came to the development of a new therapy for hypophosphatemic diseases. Still, there are many unanswered questions concerning FGF23.

Sclerostin, the product of the SOST gene has primarily been studied for its profound impact on bone mass. By interacting with LRP5 and LRP6, the glycoprotein suppresses the propagation of Wnt signals to β-catenin and thereby suppresses new bone formation. In this review, we discuss emerging data which suggest that sclerostin also acts outside the skeleton to influence metabolism. In humans, serum sclerostin levels are associated with body mass index and indices of metabolic function. Likewise, genetic mouse models of Sost gene deficiency indicate sclerostin influences adipocyte development and insulin signaling. These data raise the possibility that sclerostin neutralization may be effective at treating two epidemic conditions: osteoporosis and obesity.

Natural menopause typically occurs between the ages of 46–55 years. Premature ovarian insufficiency or premature menopause results from compromised ovarian follicular activity, occurring spontaneously or because of medical interventions, prior to the age of 40 years. The premature loss of estrogen leads to bothersome menopause symptoms and predisposes the women to multiple long-term health risks including a higher mortality risk. Hormone replacement therapy used until the natural age of menopause can help manage the symptoms effectively, and can mitigate the long-term risk of estrogen deprivation. However, hormone replacement therapy is underutilized in this population due to the inappropriate extrapolation of potential risks observed with hormone therapy use in women after natural menopause. There is a large unmet need for educating patients and providers regarding the impact of premature ovarian insufficiency and its appropriate management.

Midlife in women typically includes the menopausal transition, a time of hormonal transformation, adaptation, and reorganization. Coincident with this dynamic period of physiological change, there are putatively modifiable factors that influence disease, short-term and long-term health outcomes, symptom emergence, and longevity. The menopause transition could be considered a window of vulnerability; however, it is also a window of opportunity for intervention. Thus, the menopause transition is a critical sensitive window whereby there is opportunity for turning points for healthy aging trajectories. Preclinical research can aid in this pursuit of scientific discovery for modifiable factors and treatments, and their particular parameters. Rodent menopause models include surgical and transitional variations, allowing detection of precise determinants impacting menopause-related outcomes. These models permit systematic manipulation of endogenous and exogenous hormone exposures across the lifespan, with infinite outcome measurements ranging from molecular to behavioral. This research is uniquely poised to address complex, interactive hypotheses with extensive control in a relatively short timeframe, including dissociation of age and menopause effects. To understand the many dynamic changes with menopause, iterative and reciprocal communication between clinical and preclinical domains of science is key.

Glucocorticoids are pleiotropic hormones with potent regulatory roles in tissue homeostasis, electrolyte balance, immune defence, central nervous function, stress response, growth and development, as well as fuel metabolism. Clinically, glucocorticoids are widely used for their unsurpassed anti-inflammatory and immunomodulatory effects. However, chronic exposure to excessive levels of endogenous or exogenous glucocorticoids causes insulin resistance, glucose intolerance, dyslipidaemia, central obesity, muscle wasting and bone loss. Topical studies in rodents have demonstrated that the effects of chronic hypercortisolism on systemic fuel metabolism and body composition are in part mediated through their actions on osteoblasts. Interestingly, targeted abrogation of glucocorticoid signalling in osteoblasts also attenuates the effects of high fat intake as well as ageing on body composition and systemic fuel metabolism. Here we briefly review the physiology of glucocorticoid action and discuss emerging concepts regarding the molecular mechanisms underlying the adverse effects of glucocorticoid excess.