Parathyroid Hormone in the Regulation of Bone Growth and Resorption in Health and Disease

2021 ◽  
Vol 76 (5) ◽  
pp. 506-517
Author(s):  
Maria V. Vorontsova ◽  
Konstantin Y. Kulebyakin ◽  
Nadezhda V. Makazan ◽  
Leila S. Sozaeva ◽  
Pyotr A. Tyurin-Kuzmin
Keyword(s):  
Parathyroid Hormone ◽  
Bone Tissue ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Bone Growth ◽  
The Body ◽  
Signaling Cascades ◽  
Main Body ◽  
Bone Homeostasis ◽  
Cellular Mechanisms

Parathyroid hormone (PTH) is a key hormone responsible for regulation of calcium homeostasis in the body. Since the main body calcium depot is bone tissue, PTH has a decisive effect on its homeostasis. In this case, the hormone can activate both bone formation and resorption. Thus, PTH can ensure the conjugation of anabolic and catabolic processes, which is necessary for the renewal of bone tissue, which is had to function under constant mechanical stress. At the same time, the use of PTH in medical practice is rather small, despite its high potential as a basis for the treatment of various pathologies associated with impaired bone homeostasis. Presented review, describes the intracellular signaling cascades and molecular mechanisms that underlie the action of PTH on bone tissue cells, and intracellular signaling cascades are described. A separate section examines the cellular mechanisms of the action of PTH on bone homeostasis, discusses how the effect of the hormone on different types of cells provides an interface between the processes of synthesis and resorption. In addition, the review examines diseases associated with impaired bone homeostasis, as well as the role of PTH and impaired signaling in their etiology.

scholarly journals Molecular Mechanisms of Cardiac Remodeling and Regeneration in Physical Exercise

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1128 ◽  
Author(s):  
Dominik Schüttler ◽  
Sebastian Clauss ◽  
Ludwig T. Weckbach ◽  
Stefan Brunner
Keyword(s):  
Cardiac Function ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Cardiac Tissue ◽  
Mammalian Target Of Rapamycin ◽  
Cellular Mechanisms ◽  
Innovative Strategies ◽  
Muscle Strengthening ◽  
Positive Effects ◽  
Exercise Induced

Regular physical activity with aerobic and muscle-strengthening training protects against the occurrence and progression of cardiovascular disease and can improve cardiac function in heart failure patients. In the past decade significant advances have been made in identifying mechanisms of cardiomyocyte re-programming and renewal including an enhanced exercise-induced proliferational capacity of cardiomyocytes and its progenitor cells. Various intracellular mechanisms mediating these positive effects on cardiac function have been found in animal models of exercise and will be highlighted in this review. 1) activation of extracellular and intracellular signaling pathways including phosphatidylinositol 3 phosphate kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR), EGFR/JNK/SP-1, nitric oxide (NO)-signaling, and extracellular vesicles; 2) gene expression modulation via microRNAs (miR), in particular via miR-17-3p and miR-222; and 3) modulation of cardiac cellular metabolism and mitochondrial adaption. Understanding the cellular mechanisms, which generate an exercise-induced cardioprotective cellular phenotype with physiological hypertrophy and enhanced proliferational capacity may give rise to novel therapeutic targets. These may open up innovative strategies to preserve cardiac function after myocardial injury as well as in aged cardiac tissue.

scholarly journals Phosphorylation Sites in Protein Kinases and Phosphatases Regulated by Formyl Peptide Receptor 2 Signaling

2020 ◽  
Vol 21 (11) ◽  
pp. 3818
Author(s):  
Maria Carmela Annunziata ◽  
Melania Parisi ◽  
Gabriella Esposito ◽  
Gabriella Fabbrocini ◽  
Rosario Ammendola ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinases ◽  
Protein Phosphatase ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Fine Tuning ◽  
Formyl Peptide Receptor ◽  
Signaling Cascades ◽  
Regulatory Subunit ◽  
Formyl Peptides

FPR1, FPR2, and FPR3 are members of Formyl Peptides Receptors (FPRs) family belonging to the GPCR superfamily. FPR2 is a low affinity receptor for formyl peptides and it is considered the most promiscuous member of this family. Intracellular signaling cascades triggered by FPRs include the activation of different protein kinases and phosphatase, as well as tyrosine kinase receptors transactivation. Protein kinases and phosphatases act coordinately and any impairment of their activation or regulation represents one of the most common causes of several human diseases. Several phospho-sites has been identified in protein kinases and phosphatases, whose role may be to expand the repertoire of molecular mechanisms of regulation or may be necessary for fine-tuning of switch properties. We previously performed a phospho-proteomic analysis in FPR2-stimulated cells that revealed, among other things, not yet identified phospho-sites on six protein kinases and one protein phosphatase. Herein, we discuss on the selective phosphorylation of Serine/Threonine-protein kinase N2, Serine/Threonine-protein kinase PRP4 homolog, Serine/Threonine-protein kinase MARK2, Serine/Threonine-protein kinase PAK4, Serine/Threonine-protein kinase 10, Dual specificity mitogen-activated protein kinase kinase 2, and Protein phosphatase 1 regulatory subunit 14A, triggered by FPR2 stimulation. We also describe the putative FPR2-dependent signaling cascades upstream to these specific phospho-sites.

Abnormalities of IGF-I signaling in the pathogenesis of diseases of the bone, brain, and fetoplacental unit in humans

2008 ◽  
Vol 295 (5) ◽  
pp. E991-E999 ◽  
Author(s):  
Luigi Laviola ◽  
Annalisa Natalicchio ◽  
Sebastio Perrini ◽  
Francesco Giorgino
Keyword(s):  
Neurodegenerative Disorders ◽  
Intracellular Signaling ◽  
Bone Growth ◽  
Muscle Metabolism ◽  
Signaling Cascades ◽  
Tissue Formation ◽  
Cellular Effects ◽  
Prenatal Growth ◽  
Igf I ◽  
Review Current

IGF-I action is essential for the regulation of tissue formation and remodeling, bone growth, prenatal growth, brain development, and muscle metabolism. Cellular effects of IGF-I are mediated through the IGF-I receptor, a transmembrane tyrosine kinase that phosphorylates intracellular substrates, resulting in the activation of multiple intracellular signaling cascades. Dysregulation of IGF-I actions due to impairment in the postreceptor signaling machinery may contribute to multiple diseases in humans. This article will review current information on IGF-I signaling and illustrate recent results demonstrating how impaired IGF-I signaling and action may contribute to the pathogenesis of human diseases, including osteoporosis, neurodegenerative disorders, and reduced fetal growth in utero.

scholarly journals STAT3 controls myeloid progenitor growth during emergency granulopoiesis

Blood ◽  
2010 ◽  
Vol 116 (14) ◽  
pp. 2462-2471 ◽  
Author(s):  
Huiyuan Zhang ◽  
Hoainam Nguyen-Jackson ◽  
Athanasia D. Panopoulos ◽  
Haiyan S. Li ◽  
Peter J. Murray ◽  
...  
Keyword(s):  
Intracellular Signaling ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Signaling Cascades ◽  
Regulation Of Transcription ◽  
Conditional Deletion ◽  
Myeloid Progenitor ◽  
Enhancer Binding Protein ◽  
Transcription 3

Abstract Granulocyte colony-stimulating factor (G-CSF) mediates “emergency” granulopoiesis during infection, a process that is mimicked by clinical G-CSF use, yet we understand little about the intracellular signaling cascades that control demand-driven neutrophil production. Using a murine model with conditional deletion of signal transducer and activator of transcription 3 (STAT3) in bone marrow, we investigated the cellular and molecular mechanisms of STAT3 function in the emergency granulopoiesis response to G-CSF administration or infection with Listeria monocytogenes, a pathogen that is restrained by G-CSF signaling in vivo. Our results show that STAT3 deficiency renders hematopoietic progenitor cells and myeloid precursors refractory to the growth-promoting functions of G-CSF or L monocytogenes infection. STAT3 is necessary for accelerating granulocyte cell-cycle progression and maturation in response to G-CSF. STAT3 directly controls G-CSF–dependent expression of CCAAT-enhancer-binding protein β (C/EBPβ), a crucial factor in the emergency granulopoiesis response. Moreover, STAT3 and C/EBPβ coregulate c-Myc through interactions with the c-myc promoter that control the duration of C/EBPα occupancy during demand-driven granulopoiesis. These results place STAT3 as an essential mediator of emergency granulopoiesis by its regulation of transcription factors that direct G-CSF–responsive myeloid progenitor expansion.

scholarly journals Mechanical stimulus alters conformation of type 1 parathyroid hormone receptor in bone cells

2009 ◽  
Vol 296 (6) ◽  
pp. C1391-C1399 ◽  
Author(s):  
Yan-Liang Zhang ◽  
John A. Frangos ◽  
Mirianas Chachisvilis
Keyword(s):  
Plasma Membrane ◽  
Parathyroid Hormone ◽  
Molecular Mechanisms ◽  
Bone Growth ◽  
Fluid Shear Stress ◽  
Bone Cells ◽  
Single Cells ◽  
Conformational Transitions ◽  
Fret Efficiency

The molecular mechanisms by which bone cells transduce mechanical stimuli into intracellular biochemical responses have yet to be established. There is evidence that mechanical stimulation acts synergistically with parathyroid hormone PTH(1-34) in mediating bone growth. Using picosecond time-resolved fluorescence microscopy and G protein-coupled receptor conformation-sensitive fluorescence resonance energy transfer (FRET), we investigated conformational transitions in parathyroid hormone type 1 receptor (PTH1R). 1) A genetically engineered PTH1R sensor containing an intramolecular FRET pair was constructed that enabled detection of conformational activity of PTH1R in single cells. 2) The nature of ligand-dependent conformational change of PTH1R depends on the type of ligand: stimulation with the PTH(1-34) leads to conformational transitions characterized by decrease in FRET efficiency while NH2-terminal truncated ligand PTH(3-34) stimulates conformational transitions characterized by higher FRET efficiencies. 3) Stimulation of murine preosteoblastic cells (MC3T3-E1) with fluid shear stress (FSS) leads to significant changes in conformational equilibrium of the PTH1R in MC3T3-E1 cells, suggesting that mechanical perturbation of the plasma membrane leads to ligand-independent response of the PTH1R. Conformational transitions induced by mechanical stress were characterized by an increase in FRET efficiency, similar to those induced by the NH2-terminal truncated ligand PTH(3-34). The response to the FSS stimulation was inhibited in the presence of PTH(1-34) in the flow medium. These results indicate that the FSS can modulate the action of the PTH(1-34) ligand. 4) Plasma membrane fluidization using benzyl alcohol or cholesterol extraction also leads to conformational transitions characterized by increased FRET levels. We therefore suggest that PTH1R is involved in mediating primary mechanochemical signal transduction in MC3T3-E1 cells.

scholarly journals The Potential of FGF-2 in Craniofacial Bone Tissue Engineering: A Review

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 932
Author(s):  
Anita Novais ◽  
Eirini Chatzopoulou ◽  
Catherine Chaussain ◽  
Caroline Gorin
Keyword(s):  
Tissue Engineering ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Current Knowledge ◽  
The Body ◽  
Bone Homeostasis ◽  
Craniofacial Bone ◽  
Bone Damage ◽  
Large Bone ◽  
Large Bone Defects

Bone is a hard-vascularized tissue, which renews itself continuously to adapt to the mechanical and metabolic demands of the body. The craniofacial area is prone to trauma and pathologies that often result in large bone damage, these leading to both aesthetic and functional complications for patients. The “gold standard” for treating these large defects is autologous bone grafting, which has some drawbacks including the requirement for a second surgical site with quantity of bone limitations, pain and other surgical complications. Indeed, tissue engineering combining a biomaterial with the appropriate cells and molecules of interest would allow a new therapeutic approach to treat large bone defects while avoiding complications associated with a second surgical site. This review first outlines the current knowledge of bone remodeling and the different signaling pathways involved seeking to improve our understanding of the roles of each to be able to stimulate or inhibit them. Secondly, it highlights the interesting characteristics of one growth factor in particular, FGF-2, and its role in bone homeostasis, before then analyzing its potential usefulness in craniofacial bone tissue engineering because of its proliferative, pro-angiogenic and pro-osteogenic effects depending on its spatial-temporal use, dose and mode of administration.

scholarly journals Extracellular and Intracellular Signaling for Neuronal Polarity

2015 ◽  
Vol 95 (3) ◽  
pp. 995-1024 ◽  
Author(s):  
Takashi Namba ◽  
Yasuhiro Funahashi ◽  
Shinichi Nakamuta ◽  
Chundi Xu ◽  
Tetsuya Takano ◽  
...  
Keyword(s):  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Culture Conditions ◽  
The Body ◽  
Neuronal Polarity ◽  
Cultured Neurons ◽  
Extrinsic Factors ◽  
Major Question ◽  
Neuronal Polarization

Neurons are one of the highly polarized cells in the body. One of the fundamental issues in neuroscience is how neurons establish their polarity; therefore, this issue fascinates many scientists. Cultured neurons are useful tools for analyzing the mechanisms of neuronal polarization, and indeed, most of the molecules important in their polarization were identified using culture systems. However, we now know that the process of neuronal polarization in vivo differs in some respects from that in cultured neurons. One of the major differences is their surrounding microenvironment; neurons in vivo can be influenced by extrinsic factors from the microenvironment. Therefore, a major question remains: How are neurons polarized in vivo? Here, we begin by reviewing the process of neuronal polarization in culture conditions and in vivo. We also survey the molecular mechanisms underlying neuronal polarization. Finally, we introduce the theoretical basis of neuronal polarization and the possible involvement of neuronal polarity in disease and traumatic brain injury.

scholarly journals Molecular and Cellular Mechanisms of Melatonin in Osteosarcoma

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1618 ◽  
Author(s):  
Ko-Hsiu Lu ◽  
Renn-Chia Lin ◽  
Jia-Sin Yang ◽  
Wei-En Yang ◽  
Russel J. Reiter ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Bone Growth ◽  
Age Distribution ◽  
Underlying Mechanism ◽  
Therapeutic Effects ◽  
Anticancer Activities ◽  
Cellular Mechanisms ◽  
Wide Range ◽  
Review Reports

Osteosarcoma, the most common primary bone malignancy, occurs most frequently in adolescents with a peak of incidence at 11–15 years. Melatonin, an indole amine hormone, shows a wide range of anticancer activities. The decrease in melatonin levels simultaneously concurs with the increase in bone growth and the peak age distribution of osteosarcoma during puberty, so melatonin has been utilized as an adjunct to chemotherapy to improve the quality of life and clinical outcomes. While a large amount of research has been conducted to understand the complex pleiotropic functions and the molecular and cellular actions elicited by melatonin in various types of cancers, a few review reports have focused on osteosarcoma. Herein, we summarized the anti-osteosarcoma effects of melatonin and its underlying molecular mechanisms to illustrate the known significance of melatonin in osteosarcoma and to address cellular signaling pathways of melatonin in vitro and in animal models. Even in the same kind of osteosarcoma, melatonin has been sparingly investigated to counteract tumor growth, apoptosis, and metastasis through different mechanisms, depending on different cell lines. We highlighted the underlying mechanism of anti-osteosarcoma properties evoked by melatonin, including antioxidant activity, anti-proliferation, induction of apoptosis, and the inhibition of invasion and metastasis. Moreover, we discussed the drug synergy effects of the role of melatonin involved and the method to fortify the anti-cancer effects on osteosarcoma. As a potential therapeutic agent, melatonin is safe for children and adolescents and is a promising candidate for an adjuvant by reinforcing the therapeutic effects and abolishing the unwanted consequences of chemotherapies.

scholarly journals Intestinal Fructose and Glucose Metabolism in Health and Disease

Nutrients ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 94 ◽  
Author(s):  
Beatriz Merino ◽  
Cristina M. Fernández-Díaz ◽  
Irene Cózar-Castellano ◽  
German Perdomo
Keyword(s):  
Glucose Metabolism ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Sugar Metabolism ◽  
Sugar Consumption ◽  
Cellular Mechanisms ◽  
Obesity And Diabetes ◽  
Health And Disease ◽  
Dietary Sugars

The worldwide epidemics of obesity and diabetes have been linked to increased sugar consumption in humans. Here, we review fructose and glucose metabolism, as well as potential molecular mechanisms by which excessive sugar consumption is associated to metabolic diseases and insulin resistance in humans. To this end, we focus on understanding molecular and cellular mechanisms of fructose and glucose transport and sensing in the intestine, the intracellular signaling effects of dietary sugar metabolism, and its impact on glucose homeostasis in health and disease. Finally, the peripheral and central effects of dietary sugars on the gut–brain axis will be reviewed.

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