Fibroblast Growth Factors ; metabolism ; Humans ; Phosphorus ; metabolism

The last decade has seen an exponential increase in our understanding of osteocytes function and biology. These cells, once considered inert by-standers trapped into the mineralized bone, has now risen to be key regulators of skeletal metabolism, mineral homeostasis, and hematopoiesis. As tools and techniques to study osteocytes improved and expanded, it has become evident that there is more to these cells than initially thought. Osteocytes are now recognized not only as the key responders to mechanical forces but also as orchestrators of bone remodeling and mineral homeostasis. These cells are the primary source of several important proteins, such as sclerostin and fibroblast growth factor 23, that are currently target as novel therapies for bone loss (as the case for antisclerostin antibodies) or phosphate disorders. Better understanding of the intricate cellular and molecular mechanisms that govern osteocyte biology will open new avenue of research and ultimately indentify novel therapeutics to treat bone and mineral disorders. This review summarizes novel findings and discusses future avenues of research.
Biology ; Bone Remodeling ; Fibroblast Growth Factors ; Hematopoiesis ; Homeostasis ; Metabolism ; Osteocytes*

The last decade has seen an exponential increase in our understanding of osteocytes function and biology. These cells, once considered inert by-standers trapped into the mineralized bone, has now risen to be key regulators of skeletal metabolism, mineral homeostasis, and hematopoiesis. As tools and techniques to study osteocytes improved and expanded, it has become evident that there is more to these cells than initially thought. Osteocytes are now recognized not only as the key responders to mechanical forces but also as orchestrators of bone remodeling and mineral homeostasis. These cells are the primary source of several important proteins, such as sclerostin and fibroblast growth factor 23, that are currently target as novel therapies for bone loss (as the case for antisclerostin antibodies) or phosphate disorders. Better understanding of the intricate cellular and molecular mechanisms that govern osteocyte biology will open new avenue of research and ultimately indentify novel therapeutics to treat bone and mineral disorders. This review summarizes novel findings and discusses future avenues of research.
Biology ; Bone Remodeling ; Fibroblast Growth Factors ; Hematopoiesis ; Homeostasis ; Metabolism ; Osteocytes*

The morbidity and mortality of cardiovascular diseases (CVDs) are increasing worldwide and seriously threaten human life and health. Fibroblast growth factor 21 (FGF21), a metabolic regulator, regulates glucose and lipid metabolism and may exert beneficial effects on the cardiovascular system. In recent years, FGF21 has been found to act directly on the cardiovascular system and may be used as an early biomarker of CVDs. The present review highlights the recent progress in understanding the relationship between FGF21 and CVDs including coronary heart disease, myocardial ischemia, cardiomyopathy, and heart failure and also explores the related mechanism of the cardioprotective effect of FGF21. FGF21 plays an important role in the prediction, treatment, and improvement of prognosis in CVDs. This cardioprotective effect of FGF21 may be achieved by preventing endothelial dysfunction and lipid accumulating, inhibiting cardiomyocyte apoptosis and regulating the associated oxidative stress, inflammation and autophagy. In conclusion, FGF21 is a promising target for the treatment of CVDs, however, its clinical application requires further clarification of the precise role of FGF21 in CVDs.
Cardiovascular Diseases ; Fibroblast Growth Factors ; Humans ; Lipid Metabolism ; Oxidative Stress

Fibroblast growth factor 21 (FGF21) is a growth factor with endocrine function in the fibroblast growth factor family. Previous reports have shown that FGF21 is involved in the regulation of energy metabolism and plays a protective role in cardiovascular diseases such as coronary heart disease, diabetes, non-alcoholic fatty liver disease and so on. Recent studies have found that FGF21 can induce autophagy in a variety of tissues and organs, and autophagy is involved in many pathological processes of cardiovascular diseases, including vascular calcification, atherosclerosis, and myocardial ischemia-reperfusion injury. Therefore, FGF21 may play a protective role in a variety of cardiovascular diseases by regulating autophagy. This article reviews the research progress on the protective role of FGF21 in cardiovascular diseases by inducing autophagy.
Autophagy/physiology* ; Cardiovascular Diseases/metabolism* ; Fibroblast Growth Factors/metabolism* ; Humans ; Myocardial Reperfusion Injury/metabolism*

Fibroblast growth factor 23 (FGF23) is a hormone that is mainly secreted by osteocytes and osteoblasts in bone. The critical role of FGF23 in mineral ion homeostasis was first identified in human genetic and acquired rachitic diseases and has been further characterised in animal models. Recent studies have revealed that the levels of FGF23 increase significantly at the very early stages of chronic kidney disease (CKD) and may play a critical role in mineral ion disorders and bone metabolism in these patients. Our recent publications have also shown that FGF23 and its cofactor, Klotho, may play an independent role in directly regulating bone mineralisation instead of producing a systematic effect. In this review, we will discuss the new role of FGF23 in bone mineralisation and the pathophysiology of CKD-related bone disorders.
Calcification, Physiologic ; Fibroblast Growth Factors ; biosynthesis ; metabolism ; physiology ; Glucuronidase ; metabolism ; Humans

Elevated fibroblast growth factor 23 (FGF23) in X-linked hypophosphatemia (XLH) results in rickets and phosphate wasting, manifesting by severe bone and dental abnormalities. Burosumab, a FGF23-neutralizing antibody, an alternative to conventional treatment (phosphorus and active vitamin D analogs), showed significant improvement in the long bone phenotype. Here, we examined whether FGF23 antibody (FGF23-mAb) also improved the dentoalveolar features associated with XLH. Four-week-old male Hyp mice were injected weekly with 4 or 16 mg·kg^-1 of FGF23-mAb for 2 months and compared to wild-type (WT) and vehicle (PBS) treated Hyp mice (n = 3-7 mice). Micro-CT analyses showed that both doses of FGF23-mAb restored dentin/cementum volume and corrected the enlarged pulp volume in Hyp mice, the higher concentration resulting in a rescue similar to WT levels. FGF23-mAb treatment also improved alveolar bone volume fraction and mineral density compared to vehicle-treated ones. Histology revealed improved mineralization of the dentoalveolar tissues, with a decreased amount of osteoid, predentin and cementoid. Better periodontal ligament attachment was also observed, evidenced by restoration of the acellular cementum. These preclinical data were consistent with the retrospective analysis of two patients with XLH showing that burosumab treatment improved oral features. Taken together, our data show that the dentoalveolar tissues are greatly improved by FGF23-mAb treatment, heralding its benefit in clinics for dental abnormalities.
Humans ; Male ; Mice ; Animals ; Familial Hypophosphatemic Rickets/pathology* ; Fibroblast Growth Factor-23 ; Retrospective Studies ; Fibroblast Growth Factors/metabolism* ; Bone and Bones/metabolism* ; Phosphates/therapeutic use*

Fibroblast growth factor 21 (FGF21) is an atypical member of the FGF family. Acting in an endocrine fashion, it increases glucose uptake, modulates lipid metabolism, and sensitizes insulin response in metabolically active organs, including the liver and adipose tissue. Emerging evidence shows a strong correlation between circulating FGF21 levels and the incidence and severity of atherosclerosis. Animal studies have demonstrated a beneficial role of FGF21 in protecting against aberrant lipid profile, while recent development in FGF21 mimetics has provided further insight into the lipid-lowering effects of FGF21 signaling. The present review summarizes the physiological roles of FGF21, and discusses major breakthroughs and limitations of FGF21 mimetic-based therapeutic strategies for treating atherosclerosis.
Adipose Tissue ; Animals ; Atherosclerosis* ; Dyslipidemias ; Fibroblast Growth Factors* ; Fibroblasts* ; Glucose ; Humans ; Incidence ; Insulin ; Lipid Metabolism ; Liver

Fibroblast growth factor 21 (FGF21) is an attractive target for treating metabolic disease due to its wide-ranging beneficial effects on glucose and lipid metabolism. Circulating FGF21 levels are increased in insulin-resistant states; however, endogenous FGF21 fails to improve glucose and lipid metabolism in obesity, suggesting that metabolic syndrome is an FGF21-resistant state. Therefore, transcription factors for FGF21 are potential drug targets that could increase FGF21 expression in obesity and reduce FGF21 resistance. Despite many studies on the metabolic effects of FGF21, the transcriptional regulation of FGF21 gene expression remains controversial and is not fully understood. As the FGF21 transcription factor pathway is one of the most promising targets for the treatment of metabolic syndrome, further investigation of FGF21 transcriptional regulation is required.
Diabetes Mellitus ; Fibroblast Growth Factors* ; Gene Expression ; Glucose ; Insulin Resistance ; Lipid Metabolism ; Metabolic Diseases ; Obesity ; Transcription Factors

Fibroblast growth factors (FGF) are a group of structurally related polypeptides which constitute an elaborate signaling system with their receptors. Evidence accumulated in the years suggests that the FGF family plays a key role in the repair of central nervous system injury. The main protective mechanisms include activating the expression of PI3K-Akt, peroxisome proliferator-activated receptor (PPARγ) and other signals; inhibiting NF-κB-mediated inflammatory response, oxidative stress and apoptosis; regulating neuronal differentiation and neuronal excitability as well as participating in protection of neurovascular units and nerve function repair. This paper comprehensively summarizes the latest research progress in FGF signaling related to diseases of the central nervous system such as cerebral infarction, cerebral hemorrhage, traumatic brain injury, Alzheimer's disease, Parkinson's disease, epilepsy and depression, aiming to provide scientific basis and reference for the development of innovative FGF drugs for the prevention and treatment of neurological diseases.
Humans ; Fibroblast Growth Factors ; Phosphatidylinositol 3-Kinases/metabolism* ; Central Nervous System/metabolism* ; Signal Transduction/physiology* ; Alzheimer Disease