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Current Osteoporosis Reports Feb 2022Osteoblasts are responsible for bone matrix production during bone development and homeostasis. Much is known about the transcriptional regulation and signaling pathways... (Review)
Review
PURPOSE OF REVIEW
Osteoblasts are responsible for bone matrix production during bone development and homeostasis. Much is known about the transcriptional regulation and signaling pathways governing osteoblast differentiation. However, less is known about how osteoblasts obtain or utilize nutrients to fulfill the energetic demands associated with osteoblast differentiation and bone matrix synthesis. The goal of this review is to highlight and discuss what is known about the role and regulation of bioenergetic metabolism in osteoblasts with a focus on more recent studies.
RECENT FINDINGS
Bioenergetic metabolism has emerged as an important regulatory node in osteoblasts. Recent studies have begun to identify the major nutrients and bioenergetic pathways favored by osteoblasts as well as their regulation during differentiation. Here, we highlight how osteoblasts obtain and metabolize glucose, amino acids, and fatty acids to provide energy and other metabolic intermediates. In addition, we highlight the signals that regulate nutrient uptake and metabolism and focus on how energetic metabolism promotes osteoblast differentiation. Bioenergetic metabolism provides energy and other metabolites that are critical for osteoblast differentiation and activity. This knowledge contributes to a more comprehensive understanding of osteoblast biology and may inform novel strategies to modulate osteoblast differentiation and bone anabolism in patients with bone disorders.
Topics: Bone Development; Cell Differentiation; Energy Metabolism; Humans; Osteoblasts; Osteogenesis
PubMed: 35112289
DOI: 10.1007/s11914-022-00721-2 -
Bone May 2023Although osteoblasts and osteocytes are descended from the same lineage, they each have unique and essential roles in bone. Targeting gene deletion to osteoblasts and... (Review)
Review
Although osteoblasts and osteocytes are descended from the same lineage, they each have unique and essential roles in bone. Targeting gene deletion to osteoblasts and osteocytes using the Cre/loxP system has greatly increased our current understanding of how these cells function. Additionally, the use of the Cre/loxP system in conjunction with cell-specific reporters has enabled lineage tracing of these bone cells both in vivo and ex vivo. However, concerns have been raised regarding the specificity of the promoters used and the resulting off-target effects on cells within and outside of the bone. In this review, we have summarized the main mouse models that have been used to determine the functions of specific genes in osteoblasts and osteocytes. We discuss the expression patterns and specificity of the different promoter fragments during osteoblast to osteocyte differentiation in vivo. We also highlight how their expression in non-skeletal tissues may complicate the interpretation of study results. A thorough understanding of when and where these promoters are activated will enable improved study design and greater confidence in data interpretation.
Topics: Animals; Mice; Osteocytes; Osteoblasts; Bone and Bones; Cell Differentiation
PubMed: 36868508
DOI: 10.1016/j.bone.2023.116724 -
Biological Reviews of the Cambridge... Feb 2018Bone formation, for example during bone remodelling or fracture repair, requires mature osteoblasts to deposit bone with remarkable spatial precision. As osteoblast... (Review)
Review
Bone formation, for example during bone remodelling or fracture repair, requires mature osteoblasts to deposit bone with remarkable spatial precision. As osteoblast precursors derive either from circulation or resident stem cell pools, they and their progeny are required to migrate within the three-dimensional bone space and to navigate to their destination, i.e. to the site of bone formation. An understanding of this process is emerging based on in vitro and in vivo studies of several vertebrate species. Receptors on the osteoblast surface mediate cell adhesion and polarization, which induces osteoblast migration. Osteoblast migration is then facilitated along gradients of chemoattractants. The latter are secreted or released proteolytically by several cell types interacting with osteoblasts, including osteoclasts and vascular endothelial cells. The positions of these cellular sources of chemoattractants in relation to the position of the osteoblasts provide the migrating osteoblasts with tracks to their destination, and osteoblasts possess the means to follow a track marked by multiple chemoattractant gradients. In addition to chemotactic cues, osteoblasts sense other classes of signals and utilize them as landmarks for navigation. The composition of the osseous surface guides adhesion and hence migration efficiency and can also provide steering through haptotaxis. Further, it is likely that signals received from surface interactions modulate chemotaxis. Besides the nature of the surface, mechanical signals such as fluid flow may also serve as navigation signals for osteoblasts. Alterations in osteoblast migration and navigation might play a role in metabolic bone diseases such as osteoporosis.
Topics: Animals; Bone and Bones; Osteoblasts; Vertebrates
PubMed: 28631442
DOI: 10.1111/brv.12345 -
Current Osteoporosis Reports Dec 2014Osteoblasts, the chief bone-making cells in the body, are a focus of osteoporosis research. Although teriparatide, a synthetic fragment of the human parathyroid hormone... (Review)
Review
Osteoblasts, the chief bone-making cells in the body, are a focus of osteoporosis research. Although teriparatide, a synthetic fragment of the human parathyroid hormone (PTH), has been an effective bone anabolic drug, there remains a clinical need for additional therapeutics that safely stimulates osteoblast number and function. Work in the past several decades has provided unprecedented clarity about the roles of growth factors and transcription factors in regulating osteoblast differentiation and activity, but whether these factors may regulate cellular metabolism to influence cell fate and function has been largely unexplored. The past few years have witnessed a resurgence of interest in the cellular metabolism of osteoblasts, with the hope that elucidation of their metabolic profile may open new avenues for developing bone anabolic agents. Here we review the current understanding about glucose metabolism in osteoblasts.
Topics: Animals; Cell Differentiation; Glucose; Humans; Models, Animal; Osteoblasts; Osteogenesis; Parathyroid Hormone
PubMed: 25200872
DOI: 10.1007/s11914-014-0235-y -
Current Osteoporosis Reports Apr 2015Bone adaptation to changes in mechanical stimuli occurs by adjusting bone formation and resorption by osteoblasts and osteoclasts, to maintain optimal bone mass.... (Review)
Review
Bone adaptation to changes in mechanical stimuli occurs by adjusting bone formation and resorption by osteoblasts and osteoclasts, to maintain optimal bone mass. Osteocytes coordinate the actions of these cells on the bone surface by sensing mechanical forces and producing cytokines that increase or prevent osteoblast and osteoclast differentiation and function. Channels formed by connexins (Cxs) and, in particular, connexin 43 (Cx43) in osteoblasts and osteocytes are central part of this mechanism to control bone mass. Cx43 hemichannels are opened by fluid flow and mediate the anti-apoptotic effect of mechanical stimulation in vitro, suggesting that Cx43 participates in mechanotransduction. However, mice lacking Cx43 in osteoblasts and/or osteocytes show an increased anabolic response to loading and decreased catabolic response to unloading. This evidence suggests that Cx43 channels expressed in osteoblastic cells are not required for the response to mechanical stimulation, but mediate the consequence of lack thereof. The molecular basis of these unexpected responses to mechanical stimulation is currently under investigation.
Topics: Animals; Bone and Bones; Connexin 43; Gap Junctions; Humans; In Vitro Techniques; Mechanotransduction, Cellular; Mice; Osteoblasts; Osteocytes; Osteogenesis; Stress, Mechanical
PubMed: 25616771
DOI: 10.1007/s11914-015-0255-2 -
Cellular and Molecular Life Sciences :... May 2017The adult human skeleton is a multifunctional organ undergoing continuous remodeling. Homeostasis of bone mass in a healthy adult requires an exquisite balance between... (Review)
Review
The adult human skeleton is a multifunctional organ undergoing continuous remodeling. Homeostasis of bone mass in a healthy adult requires an exquisite balance between bone resorption by osteoclasts and bone formation by osteoblasts; disturbance of such balance is the root cause for various bone disorders including osteoporosis. To develop effective and safe therapeutics to modulate bone formation, it is essential to elucidate the molecular mechanisms governing osteoblast differentiation and activity. Due to their specialized function in collagen synthesis and secretion, osteoblasts are expected to consume large amounts of nutrients. However, studies of bioenergetics and building blocks in osteoblasts have been lagging behind those of growth factors and transcription factors. Genetic studies in both humans and mice over the past 15 years have established Wnt signaling as a critical mechanism for stimulating osteoblast differentiation and activity. Importantly, recent studies have uncovered that Wnt signaling directly reprograms cellular metabolism by stimulating aerobic glycolysis, glutamine catabolism as well as fatty acid oxidation in osteoblast-lineage cells. Such findings therefore reveal an important regulatory axis between bone anabolic signals and cellular bioenergetics. A comprehensive understanding of osteoblast metabolism and its regulation is likely to reveal molecular targets for novel bone therapies.
Topics: Animals; Bone and Bones; Humans; Models, Biological; Osteoblasts; Signal Transduction; Wnt Proteins; Wnt Signaling Pathway
PubMed: 27888287
DOI: 10.1007/s00018-016-2425-5 -
Bone Oct 2018The emergence of bone as an endocrine organ able to influence whole body metabolism, together with comorbid epidemics of obesity, diabetes, and osteoporosis, have... (Review)
Review
The emergence of bone as an endocrine organ able to influence whole body metabolism, together with comorbid epidemics of obesity, diabetes, and osteoporosis, have prompted a renewed interest in the intermediary metabolism of the osteoblast. To date, most studies have focused on the utilization of glucose by this specialized cell, but the oxidation of fatty acids results in a larger energy yield. Osteoblasts express the requisite receptors and catabolic enzymes to take up and then metabolize fatty acids, which appears to be required during later stages of differentiation when the osteoblast is dedicated to matrix production and mineralization. In this article, we provide an overview of fatty acid β-oxidation and highlight studies demonstrating that the skeleton plays a significant role in the clearance of circulating lipoproteins and non-esterified fatty acids. Additionally, we review the requirement for long-chain fatty acid metabolism during post-natal bone development and the effects of anabolic stimuli on fatty acid utilization by osteoblasts. These recent findings may help to explain the skeletal manifestations of human diseases associated with impaired lipid metabolism while also providing additional insights into the metabolic requirements of skeletal homeostasis.
Topics: Animals; Fatty Acids; Humans; Lipid Metabolism; Osteoblasts
PubMed: 28863948
DOI: 10.1016/j.bone.2017.08.024 -
Journal of Cellular Physiology Nov 2017Even if osteoarthritis pathogenesis is still poorly understood, numerous evidences suggest that osteoblasts dysregulation plays a key role in osteoarthritis... (Review)
Review
Even if osteoarthritis pathogenesis is still poorly understood, numerous evidences suggest that osteoblasts dysregulation plays a key role in osteoarthritis pathogenesis. An abnormal expression of OPG and RANKL has been described in osteoarthritis osteoblasts, which is responsible for abnormal bone remodeling and decreased mineralization. Alterations in genes expression are involved in dysregulation of osteoblast function, bone remodeling, and mineralization, leading to osteoarthritis development. Moreover, osteoblasts produce numerous transcription factors, growth factors, and other proteic molecules which are involved in osteoarthritis pathogenesis.
Topics: Animals; Bone Remodeling; Disease Progression; Gene Expression Regulation; Humans; Joints; Osteoarthritis; Osteoblasts; Phenotype; Signal Transduction
PubMed: 28425564
DOI: 10.1002/jcp.25969 -
International Journal of Molecular... Jul 2021A review of the available literature was performed in order to summarize the existing evidence between osteoblast dysfunction and clinical features in non-hereditary... (Review)
Review
A review of the available literature was performed in order to summarize the existing evidence between osteoblast dysfunction and clinical features in non-hereditary sclerosing bone diseases. It has been known that proliferation and migration of osteoblasts are concerted by soluble factors such as fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), transforming growth factor (TGF), bone morphogenetic protein (BMP) but also by signal transduction cascades such as Wnt signaling pathway. Protein kinases play also a leading role in triggering the activation of osteoblasts in this group of diseases. Post-zygotic changes in mitogen-activated protein kinase (MAPK) have been shown to be associated with sporadic cases of Melorheostosis. Serum levels of FGF and PDGF have been shown to be increased in myelofibrosis, although studies focusing on Sphingosine-1-phosphate receptor was shown to be strongly expressed in Paget disease of the bone, which may partially explain the osteoblastic hyperactivity during this condition. Pathophysiological mechanisms of osteoblasts in osteoblastic metastases have been studied much more thoroughly than in rare sclerosing syndromes: striking cellular mechanisms such as osteomimicry or complex intercellular signaling alterations have been described. Further research is needed to describe pathological mechanisms by which rare sclerosing non hereditary diseases lead to osteoblast dysfunction.
Topics: Animals; Bone Morphogenetic Proteins; Fibroblast Growth Factors; Humans; MAP Kinase Signaling System; Melorheostosis; Osteoblasts; Platelet-Derived Growth Factor; Sphingosine-1-Phosphate Receptors
PubMed: 34360745
DOI: 10.3390/ijms22157980 -
International Journal of Molecular... Oct 2022Mineralization-competent cells like osteoblasts and chondrocytes release matrix vesicles (MVs) which accumulate Ca and P, creating an optimal environment for apatite...
Mineralization-competent cells like osteoblasts and chondrocytes release matrix vesicles (MVs) which accumulate Ca and P, creating an optimal environment for apatite formation. The mineralization process requires the involvement of proteins, such as annexins (Anx) and tissue-nonspecific alkaline phosphatase (TNAP), as well as low molecular-weight compounds. Apigenin, a flavonoid compound, has been reported to affect bone metabolism, but there are doubts about its mechanism of action under physiological and pathological conditions. In this report, apigenin potency to modulate annexin A6 (AnxA6)- and TNAP-mediated osteoblast mineralization was explored using three cell lines: human fetal osteoblastic hFOB 1.19, human osteosarcoma Saos-2, and human coronary artery smooth muscle cells HCASMC. We compared the mineralization competence, the morphology and composition of minerals, and the protein distribution in control and apigenin-treated cells and vesicles. The mineralization ability was monitored by AR-S/CPC analysis, and TNAP activity was determined by ELISA assay. Apigenin affected the mineral structure and modulated TNAP activity depending on the concentration. We also observed increased mineralization in Saos-2 cells. Based on TEM-EDX, we found that apigenin influenced the mineral composition. This flavonoid also disturbed the intracellular distribution of AnxA6 and TNAP, especially blocking AnxA6 aggregation and TNAP attachment to the membrane, as examined by FM analysis of cells and TEM-gold analysis of vesicles. In summary, apigenin modulates the mineralization process by regulating AnxA6 and TNAP, as well as through various effects on normal and cancer bone tissues or atherosclerotic soft tissue.
Topics: Humans; Alkaline Phosphatase; Annexin A6; Apigenin; Calcification, Physiologic; Osteoblasts
PubMed: 36361965
DOI: 10.3390/ijms232113179