scholarly journals Bone Cell Bioenergetics and Skeletal Energy Homeostasis

2017 ◽  
Vol 97 (2) ◽  
pp. 667-698 ◽  
Author(s):  
Ryan C. Riddle ◽  
Thomas L. Clemens
Keyword(s):  
Energy Homeostasis ◽  
Metabolic Diseases ◽  
Bone Cells ◽  
Bone Cell ◽  
Intermediary Metabolism ◽  
Energy Status ◽  
Health And Disease ◽  
Rising Incidence ◽  
Metabolic Properties

The rising incidence of metabolic diseases worldwide has prompted renewed interest in the study of intermediary metabolism and cellular bioenergetics. The application of modern biochemical methods for quantitating fuel substrate metabolism with advanced mouse genetic approaches has greatly increased understanding of the mechanisms that integrate energy metabolism in the whole organism. Examination of the intermediary metabolism of skeletal cells has been sparked by a series of unanticipated observations in genetically modified mice that suggest the existence of novel endocrine pathways through which bone cells communicate their energy status to other centers of metabolic control. The recognition of this expanded role of the skeleton has in turn led to new lines of inquiry directed at defining the fuel requirements and bioenergetic properties of bone cells. This article provides a comprehensive review of historical and contemporary studies on the metabolic properties of bone cells and the mechanisms that control energy substrate utilization and bioenergetics. Special attention is devoted to identifying gaps in our current understanding of this new area of skeletal biology that will require additional research to better define the physiological significance of skeletal cell bioenergetics in human health and disease.

scholarly journals Energy Metabolism of Bone

2017 ◽  
Vol 45 (7) ◽  
pp. 887-893 ◽  
Author(s):  
Katherine J. Motyl ◽  
Anyonya R. Guntur ◽  
Adriana Lelis Carvalho ◽  
Clifford J. Rosen
Keyword(s):  
Bone Remodeling ◽  
Energy Homeostasis ◽  
Bone Structure ◽  
Bone Cells ◽  
Bone Cell ◽  
Whole Body ◽  
Blood Calcium ◽  
Micro Cracks ◽  
Intimate Link ◽  
Body Energy

Biological processes utilize energy and therefore must be prioritized based on fuel availability. Bone is no exception to this, and the benefit of remodeling when necessary outweighs the energy costs. Bone remodeling is important for maintaining blood calcium homeostasis, repairing micro cracks and fractures, and modifying bone structure so that it is better suited to withstand loading demands. Osteoclasts, osteoblasts, and osteocytes are the primary cells responsible for bone remodeling, although bone marrow adipocytes and other cells may also play an indirect role. There is a renewed interest in bone cell energetics because of the potential for these processes to be targeted for osteoporosis therapies. In contrast, due to the intimate link between bone and energy homeostasis, pharmaceuticals that treat metabolic disease or have metabolic side effects often have deleterious bone consequences. In this brief review, we will introduce osteoporosis, discuss how bone cells utilize energy to function, evidence for bone regulating whole body energy homeostasis, and some of the unanswered questions and opportunities for further research in the field.

scholarly journals Update on FXR Biology: Promising Therapeutic Target?

2018 ◽  
Vol 19 (7) ◽  
pp. 2069 ◽  
Author(s):  
Chang Han
Keyword(s):  
Therapeutic Target ◽  
Energy Homeostasis ◽  
Metabolic Diseases ◽  
Current Knowledge ◽  
Farnesoid X Receptor ◽  
Metabolic Effects ◽  
Metabolic Dysfunction ◽  
Energy Status ◽  
Safety Issues ◽  
Attractive Therapeutic Target

Farnesoid X receptor (FXR), a metabolic nuclear receptor, plays critical roles in the maintenance of systemic energy homeostasis and the integrity of many organs, including liver and intestine. It regulates bile acid, lipid, and glucose metabolism, and contributes to inter-organ communication, in particular the enterohepatic signaling pathway, through bile acids and fibroblast growth factor-15/19 (FGF-15/19). The metabolic effects of FXR are also involved in gut microbiota. In addition, FXR has various functions in the kidney, adipose tissue, pancreas, cardiovascular system, and tumorigenesis. Consequently, the deregulation of FXR may lead to abnormalities of specific organs and metabolic dysfunction, allowing the protein as an attractive therapeutic target for the management of liver and/or metabolic diseases. Indeed, many FXR agonists have been being developed and are under pre-clinical and clinical investigations. Although obeticholic acid (OCA) is one of the promising candidates, significant safety issues have remained. The effects of FXR modulation might be multifaceted according to tissue specificity, disease type, and/or energy status, suggesting the careful use of FXR agonists. This review summarizes the current knowledge of systemic FXR biology in various organs and the gut–liver axis, particularly regarding the recent advancement in these fields, and also provides pharmacological aspects of FXR modulation for rational therapeutic strategies and novel drug development.

scholarly journals Bone marrow and bone: a functional unit

2002 ◽  
Vol 173 (3) ◽  
pp. 387-394 ◽  
Author(s):  
JE Compston
Keyword(s):  
Bone Marrow ◽  
Immune Cells ◽  
Bone Cells ◽  
Bone Remodelling ◽  
Functional Unit ◽  
Bone Cell ◽  
Unit Cells ◽  
Health And Disease ◽  
The Relationship ◽  
Bone Physiology

Bone and bone marrow, although often regarded as separate systems, function as a single unit. Cells in the bone marrow are the precursors of bone remodelling cells and exert an important regulatory role both on their own development and the remodelling process, acting as mediators for the effects of systemic and local factors. Other cells, such as immune cells and megakaryocytes, also contribute to the regulation of bone cell development and activity. Many diseases that affect the bone marrow have profound effects on bone, involving interactions between abnormal and normal marrow cells and those of bone. Although recent advances in bone physiology have produced new insights into the relationship between bone marrow and bone cells, much remains to be learnt about the mechanisms by which marrow and bone act in synergy to regulate bone remodelling, both in health and disease.

Rhodiola and salidroside in the treatment of metabolic disorders

2019 ◽  
Vol 19 (19) ◽  
pp. 1611-1626 ◽  
Author(s):  
Xiang-Li Bai ◽  
Xiu-Ling Deng ◽  
Guang-Jie Wu ◽  
Wen-Jing Li ◽  
Si Jin
Keyword(s):  
Metabolic Disorders ◽  
Energy Homeostasis ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Ex Vivo ◽  
Treatment Strategies ◽  
Ampk Signaling ◽  
Beneficial Effects

Over the past three decades, the knowledge gained about the mechanisms that underpin the potential use of Rhodiola in stress- and ageing-associated disorders has increased, and provided a universal framework for studies that focused on the use of Rhodiola in preventing or curing metabolic diseases. Of particular interest is the emerging role of Rhodiola in the maintenance of energy homeostasis. Moreover, over the last two decades, great efforts have been undertaken to unravel the underlying mechanisms of action of Rhodiola in the treatment of metabolic disorders. Extracts of Rhodiola and salidroside, the most abundant active compound in Rhodiola, are suggested to provide a beneficial effect in mental, behavioral, and metabolic disorders. Both in vivo and ex vivo studies, Rhodiola extracts and salidroside ameliorate metabolic disorders when administered acutely or prior to experimental injury. The mechanism involved includes multi-target effects by modulating various synergistic pathways that control oxidative stress, inflammation, mitochondria, autophagy, and cell death, as well as AMPK signaling that is associated with possible beneficial effects on metabolic disorders. However, evidence-based data supporting the effectiveness of Rhodiola or salidroside in treating metabolic disorders is limited. Therefore, a comprehensive review of available trials showing putative treatment strategies of metabolic disorders that include both clinical effective perspectives and fundamental molecular mechanisms is warranted. This review highlights studies that focus on the potential role of Rhodiola extracts and salidroside in type 2 diabetes and atherosclerosis, the two most common metabolic diseases.

scholarly journals The Role of Adipose Tissue Mitochondria: Regulation of Mitochondrial Function for the Treatment of Metabolic Diseases

2019 ◽  
Vol 20 (19) ◽  
pp. 4924 ◽  
Author(s):  
Lee ◽  
Park ◽  
Oh ◽  
Lee ◽  
Kim ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Mitochondrial Function ◽  
Energy Homeostasis ◽  
Metabolic Diseases ◽  
Oxidative Capacity ◽  
Adipose Tissues ◽  
Adaptive Thermogenesis ◽  
Brown Adipose

: Mitochondria play a key role in maintaining energy homeostasis in metabolic tissues, including adipose tissues. The two main types of adipose tissues are the white adipose tissue (WAT) and the brown adipose tissue (BAT). WAT primarily stores excess energy, whereas BAT is predominantly responsible for energy expenditure by non-shivering thermogenesis through the mitochondria. WAT in response to appropriate stimuli such as cold exposure and β-adrenergic agonist undergoes browning wherein it acts as BAT, which is characterized by the presence of a higher number of mitochondria. Mitochondrial dysfunction in adipocytes has been reported to have strong correlation with metabolic diseases, including obesity and type 2 diabetes. Dysfunction of mitochondria results in detrimental effects on adipocyte differentiation, lipid metabolism, insulin sensitivity, oxidative capacity, and thermogenesis, which consequently lead to metabolic diseases. Recent studies have shown that mitochondrial function can be improved by using thiazolidinedione, mitochondria-targeted antioxidants, and dietary natural compounds; by performing exercise; and by controlling caloric restriction, thereby maintaining the metabolic homeostasis by inducing adaptive thermogenesis of BAT and browning of WAT. In this review, we focus on and summarize the molecular regulation involved in the improvement of mitochondrial function in adipose tissues so that strategies can be developed to treat metabolic diseases.

The role of AMP-activated protein kinase in the coordination of skeletal muscle turnover and energy homeostasis

2012 ◽  
Vol 303 (5) ◽  
pp. C475-C485 ◽  
Author(s):  
Anthony M. J. Sanchez ◽  
Robin B. Candau ◽  
Alfredo Csibi ◽  
Allan F. Pagano ◽  
Audrey Raibon ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Energy Homeostasis ◽  
Therapeutic Potential ◽  
Energy Status ◽  
Muscle Plasticity ◽  
Glucose And Lipid Metabolism ◽  
Muscle Homeostasis ◽  
Amp Activated Protein Kinase

The AMP-activated protein kinase (AMPK) is a serine/threonine protein kinase that acts as a sensor of cellular energy status switch regulating several systems including glucose and lipid metabolism. Recently, AMPK has been implicated in the control of skeletal muscle mass by decreasing mTORC1 activity and increasing protein degradation through regulation of ubiquitin-proteasome and autophagy pathways. In this review, we give an overview of the central role of AMPK in the control of skeletal muscle plasticity. We detail particularly its implication in the control of the hypertrophic and atrophic signaling pathways. In the light of these cumulative and attractive results, AMPK appears as a key player in regulating muscle homeostasis and the modulation of its activity may constitute a therapeutic potential in treating muscle wasting syndromes in humans.

scholarly journals The Osteocyte: From “Prisoner” to “Orchestrator”

2021 ◽  
Vol 6 (1) ◽  
pp. 28
Author(s):  
Carla Palumbo ◽  
Marzia Ferretti
Keyword(s):  
Bone Remodeling ◽  
Bone Cells ◽  
Bone Matrix ◽  
Bone Cell ◽  
Morphological Aspects ◽  
The Matrix ◽  
Relevant Role ◽  
Mineralized Bone Matrix ◽  
Cell Signaling Pathways

Osteocytes are the most abundant bone cells, entrapped inside the mineralized bone matrix. They derive from osteoblasts through a complex series of morpho-functional modifications; such modifications not only concern the cell shape (from prismatic to dendritic) and location (along the vascular bone surfaces or enclosed inside the lacuno-canalicular cavities, respectively) but also their role in bone processes (secretion/mineralization of preosseous matrix and/or regulation of bone remodeling). Osteocytes are connected with each other by means of different types of junctions, among which the gap junctions enable osteocytes inside the matrix to act in a neuronal-like manner, as a functional syncytium together with the cells placed on the vascular bone surfaces (osteoblasts or bone lining cells), the stromal cells and the endothelial cells, i.e., the bone basic cellular system (BBCS). Within the BBCS, osteocytes can communicate in two ways: by means of volume transmission and wiring transmission, depending on the type of signals (metabolic or mechanical, respectively) received and/or to be forwarded. The capability of osteocytes in maintaining skeletal and mineral homeostasis is due to the fact that it acts as a mechano-sensor, able to transduce mechanical strains into biological signals and to trigger/modulate the bone remodeling, also because of the relevant role of sclerostin secreted by osteocytes, thus regulating different bone cell signaling pathways. The authors want to emphasize that the present review is centered on the morphological aspects of the osteocytes that clearly explain their functional implications and their role as bone orchestrators.

scholarly journals Targeted Ptpn11 deletion in mice reveals the essential role of SHP2 in osteoblast differentiation and skeletal homeostasis

Bone Research ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Lijun Wang ◽  
Huiliang Yang ◽  
Jiahui Huang ◽  
Shaopeng Pei ◽  
Liyun Wang ◽  
...  
Keyword(s):  
Bone Cells ◽  
Protein Tyrosine Phosphatases ◽  
Osteoblastic Differentiation ◽  
Bone Cell ◽  
Signaling Proteins ◽  
Tubular Bone ◽  
Skeletal Homeostasis ◽  
Underlying Mechanisms ◽  
And Function

AbstractThe maturation and function of osteoblasts (OBs) rely heavily on the reversible phosphorylation of signaling proteins. To date, most of the work in OBs has focused on phosphorylation by tyrosyl kinases, but little has been revealed about dephosphorylation by protein tyrosine phosphatases (PTPases). SHP2 (encoded by PTPN11) is a ubiquitously expressed PTPase. PTPN11 mutations are associated with both bone and cartilage manifestations in patients with Noonan syndrome (NS) and metachondromatosis (MC), although the underlying mechanisms remain elusive. Here, we report that SHP2 deletion in bone gamma-carboxyglutamate protein-expressing (Bglap+) bone cells leads to massive osteopenia in both trabecular and cortical bones due to the failure of bone cell maturation and enhanced osteoclast activity, and its deletion in Bglap+ chondrocytes results in the onset of enchondroma and osteochondroma in aged mice with increased tubular bone length. Mechanistically, SHP2 was found to be required for osteoblastic differentiation by promoting RUNX2/OSTERIX signaling and for the suppression of osteoclastogenesis by inhibiting STAT3-mediated RANKL production by osteoblasts and osteocytes. These findings are likely to explain the compromised skeletal system in NS and MC patients and to inform the development of novel therapeutics to combat skeletal disorders.

scholarly journals Sirtuins in Renal Health and Disease

2018 ◽  
Vol 29 (7) ◽  
pp. 1799-1809 ◽  
Author(s):  
Marina Morigi ◽  
Luca Perico ◽  
Ariela Benigni
Keyword(s):  
Energy Homeostasis ◽  
Kidney Diseases ◽  
Renal Physiology ◽  
Cellular Functions ◽  
Evolutionarily Conserved ◽  
Biologic Effects ◽  
Response To Stress ◽  
Health And Disease ◽  
Atp Generation

Sirtuins belong to an evolutionarily conserved family of NAD+-dependent deacetylases that share multiple cellular functions related to proliferation, DNA repair, mitochondrial energy homeostasis, and antioxidant activity. Mammalians express seven sirtuins (SIRT1–7) that are localized in different subcellular compartments. Changes in sirtuin expression are critical in several diseases, including metabolic syndrome, diabetes, cancer, and aging. In the kidney, the most widely studied sirtuin is SIRT1, which exerts cytoprotective effects by inhibiting cell apoptosis, inflammation, and fibrosis together with SIRT3, a crucial metabolic sensor that regulates ATP generation and mitochondrial adaptive response to stress. Here, we provide an overview of the biologic effects of sirtuins and the molecular targets thereof regulating renal physiology. This review also details progress made in understanding the effect of sirtuins in the pathophysiology of chronic and acute kidney diseases, highlighting the key role of SIRT1, SIRT3, and now SIRT6 as potential therapeutic targets. In this context, the current pharmacologic approaches to enhancing the activity of SIRT1 and SIRT3 will be discussed.

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