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International Journal of Molecular... Jun 2021Osteoblasts, the cells that build up our skeleton, are remarkably versatile and important cells that need tight regulation in all the phases of their differentiation to... (Review)
Review
Osteoblasts, the cells that build up our skeleton, are remarkably versatile and important cells that need tight regulation in all the phases of their differentiation to guarantee proper skeletal development and homeostasis. Although we know many of the key pathways involved in osteoblast differentiation and signaling, it is becoming clearer and clearer that this is just the tip of the iceberg, and we are constantly discovering novel concepts in osteoblast physiology. In this review, we discuss well-established pathways of osteoblastic differentiation, i.e., the classical ones committing mesenchymal stromal cells to osteoblast, and then osteocytes as well as recently emerged players. In particular, we discuss micro (mi)RNAs, long non-coding (lnc)RNAs, circular (circ)RNAs, and extracellular vesicles, focusing on the mechanisms through which osteoblasts are regulated by these factors, and conversely, how they use extracellular vesicles to communicate with the surrounding microenvironment.
Topics: Animals; Cell Differentiation; Extracellular Vesicles; Humans; MicroRNAs; Osteoblasts; RNA, Long Noncoding; Signal Transduction
PubMed: 34206294
DOI: 10.3390/ijms22136651 -
The Journal of Clinical Investigation Feb 2016Osteoblast-derived VEGF is important for bone development and postnatal bone homeostasis. Previous studies have demonstrated that VEGF affects bone repair and...
Osteoblast-derived VEGF is important for bone development and postnatal bone homeostasis. Previous studies have demonstrated that VEGF affects bone repair and regeneration; however, the cellular mechanisms by which it works are not fully understood. In this study, we investigated the functions of osteoblast-derived VEGF in healing of a bone defect. The results indicate that osteoblast-derived VEGF plays critical roles at several stages in the repair process. Using transgenic mice with osteoblast-specific deletion of Vegfa, we demonstrated that VEGF promoted macrophage recruitment and angiogenic responses in the inflammation phase, and optimal levels of VEGF were required for coupling of angiogenesis and osteogenesis in areas where repair occurs by intramembranous ossification. VEGF likely functions as a paracrine factor in this process because deletion of Vegfr2 in osteoblastic lineage cells enhanced osteoblastic maturation and mineralization. Furthermore, osteoblast- and hypertrophic chondrocyte-derived VEGF stimulated recruitment of blood vessels and osteoclasts and promoted cartilage resorption at the repair site during the periosteal endochondral ossification stage. Finally, osteoblast-derived VEGF stimulated osteoclast formation in the final remodeling phase of the repair process. These findings provide a basis for clinical strategies to improve bone regeneration and treat defects in bone healing.
Topics: Animals; Bone Regeneration; Calcification, Physiologic; Cell Differentiation; Mice; Mice, Knockout; Osteoblasts; Osteogenesis; Vascular Endothelial Growth Factor A
PubMed: 26731472
DOI: 10.1172/JCI82585 -
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 -
Medical Science Monitor : International... Apr 2018BACKGROUND LPS-inhibited osteoblastic differentiation plays an important role in the pathogenesis of osteomyelitis. Thus, searching for drugs that affect LPS-mediated...
BACKGROUND LPS-inhibited osteoblastic differentiation plays an important role in the pathogenesis of osteomyelitis. Thus, searching for drugs that affect LPS-mediated osteoblastic differentiation may be crucial in developing therapies for osteomyelitis. The purpose of this study was to investigate the role and mechanisms of resveratrol, a natural polyphenol present in red wine, on LPS-inhibited osteoblastic differentiation. MATERIAL AND METHODS Cell viability was measured by MMT assay. Mitochondrial ATP levels, membrane potential, and superoxide production were measured to evaluate the effects of LPS and resveratrol on mitochondrial functions in osteoblast-like MC3T3-E1 cells. Osteoblast-related genes, including ALP, OCN, OPN, and RUNX2, were measured by ELISA analysis and RT-PCR in differentiated osteoblast cells treated with LPS and resveratrol. Cellular Sirt1 and PCG-1α levels were measured by Western blot to probe the impact of resveratrol treatment in LPS-stimulated MC3T3-E1 osteoblasts. RESULTS The results showed that LPS caused significant mitochondrial dysfunctions of MC3T3-E1 cells in a dose-dependent manner, which were attenuated by resveratrol. Furthermore, LPS markedly decreased the expression of ALP, OCN, OPN, and RUNX2 in MC3T3-E1 cells cultivated in osteoblast differentiation medium, suggesting that LPS inhibited the osteoblastic differentiation of MC3T3-E1 cells. However, resveratrol obviously alleviated the suppressive impact of LPS on osteoblast differentiation. In addition, resveratrol increased expression of Sirt1 and PGC-1α in MC3T3-E1 cells treated with LPS. CONCLUSIONS Taken together, these results show that resveratrol alleviated the suppression of LPS on osteoblast differentiation by improving, at least in part, mitochondrial function.
Topics: 3T3 Cells; Animals; Apoptosis; Cell Differentiation; Cell Line; Cell Survival; Lipopolysaccharides; Mice; Mitochondria; Osteoblasts; Osteogenesis; Resveratrol; Stilbenes
PubMed: 29624568
DOI: 10.12659/msm.905703 -
Biomaterials Apr 2000The development of tissue engineering in the field of orthopaedic surgery is now booming. Two fields of research in particular are emerging: the association of... (Review)
Review
The development of tissue engineering in the field of orthopaedic surgery is now booming. Two fields of research in particular are emerging: the association of osteo-inductive factors with implantable materials; and the association of osteogenic stem cells with these materials (hybrid materials). In both cases, an understanding of the phenomena of cell adhesion and, in particular, understanding of the proteins involved in osteoblast adhesion on contact with the materials is of crucial importance. The proteins involved in osteoblast adhesion are described in this review (extracellular matrix proteins, cytoskeletal proteins, integrins, cadherins, etc.). During osteoblast/material interactions, their expression is modified according to the surface characteristics of materials. Their involvement in osteoblastic response to mechanical stimulation highlights the significance of taking them into consideration during development of future biomaterials. Finally, an understanding of the proteins involved in osteoblast adhesion opens up new possibilities for the grafting of these proteins (or synthesized peptide) onto vector materials, to increase their in vivo bioactivity or to promote cell integration within the vector material during the development of hybrid materials.
Topics: Animals; Biocompatible Materials; Cell Adhesion; Humans; Osteoblasts
PubMed: 10711964
DOI: 10.1016/s0142-9612(99)00242-2 -
Frontiers in Endocrinology 2020The skeleton is a dynamic and metabolically active organ with the capacity to influence whole body metabolism. This newly recognized function has propagated interest in... (Review)
Review
The skeleton is a dynamic and metabolically active organ with the capacity to influence whole body metabolism. This newly recognized function has propagated interest in the connection between bone health and metabolic dysfunction. Osteoblasts, the specialized mesenchymal cells responsible for the production of bone matrix and mineralization, rely on multiple fuel sources. The utilization of glucose by osteoblasts has long been a focus of research, however, lipids and their derivatives, are increasingly recognized as a vital energy source. Osteoblasts possess the necessary receptors and catabolic enzymes for internalization and utilization of circulating lipids. Disruption of these processes can impair osteoblast function, resulting in skeletal deficits while simultaneously altering whole body lipid homeostasis. This article provides an overview of the metabolism of postprandial and stored lipids and the osteoblast's ability to acquire and utilize these molecules. We focus on the requirement for fatty acid oxidation and the pathways regulating this function as well as the negative impact of dyslipidemia on the osteoblast and skeletal health. These findings provide key insights into the nuances of lipid metabolism in influencing skeletal homeostasis which are critical to appreciate the extent of the osteoblast's role in metabolic homeostasis.
Topics: Animals; Homeostasis; Humans; Lipids; Osteoblasts
PubMed: 33071983
DOI: 10.3389/fendo.2020.578194 -
Lasers in Medical Science Jul 2018In this study, we present a review of the literature on the impact of photobiomodulation on osteoblast-like cell culture. Searches were performed in the PubMed/MEDLINE... (Review)
Review
In this study, we present a review of the literature on the impact of photobiomodulation on osteoblast-like cell culture. Searches were performed in the PubMed/MEDLINE (Medical Literature Analysis and Retrieval System Online), SCOPUS, and SPIE digital library databases for original articles regarding the effects of LLLT on osteoblast-like cells in experimental models using LLLT published in English from the last 20 years. The search identified 1439 studies. After the analysis of the abstracts, 1409 studies were excluded and 30 studies were then selected for the full-text analysis, 8 of which were excluded. Thus, 22 studies were included for a critical evaluation of the impact of photobiomodulation on osteoblast-like cell culture. The cell lineages studied were primary rat, primary human, saos-2, Osteo-1, MC3T3, MG63, and OFCOL II. Moreover, a wide variety of experimental models were used to experimentally analyze the impact of photobiomodulation, the most common of which were alkaline phosphatase, MTT, and cell count. This review suggests that osteoblastic-like cells are susceptible to photobiomodulation but that most of the light parameters varied by different authors have little to no influence on proliferation but very high levels of irradiance have demonstrated deleterious effects on proliferation, highlighting the bi-phasic effect of photobiomodulation.
Topics: Alkaline Phosphatase; Animals; Cell Proliferation; Cells, Cultured; Humans; Low-Level Light Therapy; Osteoblasts
PubMed: 29572767
DOI: 10.1007/s10103-018-2486-9 -
Cell and Tissue Research Jan 2014Osteoblasts are specialized mesenchyme-derived cells accountable for bone synthesis, remodelling and healing. Differentiation of osteoblasts from mesenchymal stem cells... (Review)
Review
Osteoblasts are specialized mesenchyme-derived cells accountable for bone synthesis, remodelling and healing. Differentiation of osteoblasts from mesenchymal stem cells (MSC) towards osteocytes is a multi-step process strictly controlled by various genes, transcription factors and signalling proteins. The aim of this review is to provide an update on the nature of bone-forming osteoblastic cells, highlighting recent data on MSC-osteoblast-osteocyte transformation from a molecular perspective and to discuss osteoblast malfunctions in various bone diseases. We present here the consecutive stages occurring in the differentiation of osteoblasts from MSC, the transcription factors involved and the role of miRNAs in the process. Recent data concerning the pathogenic mechanisms underlying the loss of bone mass and architecture caused by malfunctions in the synthetic activity and metabolism of osteoblasts in osteoporosis, osteogenesis imperfecta, osteoarthritis and rheumatoid arthritis are discussed. The newly acquired knowledge of the ontogeny of osteoblasts will assist in unravelling the abnormalities taking place during their differentiation and will facilitate the prevention and/or treatment of bone diseases by therapy directed against altered molecules and mechanisms.
Topics: Animals; Arthritis; Bone and Bones; Humans; Mesenchymal Stem Cells; Osteoblasts; Osteocytes; Osteogenesis; Osteogenesis Imperfecta
PubMed: 24292720
DOI: 10.1007/s00441-013-1750-3 -
Journal of Cellular Biochemistry Dec 2006Runx2, osterix, and beta-catenin are essential for osteoblast differentiation. Runx2 directs multipotent mesenchymal cells to an osteoblastic lineage, and inhibits them... (Review)
Review
Runx2, osterix, and beta-catenin are essential for osteoblast differentiation. Runx2 directs multipotent mesenchymal cells to an osteoblastic lineage, and inhibits them from differentiating into the adipocytic and chondrocytic lineages. After differentiating to preosteoblasts, beta-catenin, osterix, and Runx2 direct them to immature osteoblasts, which produce bone matrix proteins, blocking their potential to differentiate into the chondrocytic lineage. Runx2 inhibits osteoblast maturation and the transition into osteocytes, keeping osteoblasts in an immature stage. Other transcription factors including Msx1, Msx2, Dlx5, Dlx6, Twist, AP1(Fos/Jun), Knox-20, Sp3, and ATF4 are also involved in osteoblast differentiation. To gain an understanding of bone development, it is important to position these transcription factors to the right places in the processes of osteoblast differentiation.
Topics: Animals; Cell Differentiation; Cell Lineage; Core Binding Factor Alpha 1 Subunit; Humans; Mice; Osteoblasts; Sp7 Transcription Factor; Transcription Factors; beta Catenin
PubMed: 16795049
DOI: 10.1002/jcb.20958 -
Biomaterials Apr 2012The demand for orthopedic and dental implants will continue to grow, and for these applications, titanium and its alloys have been used extensively. While these implants... (Review)
Review
The demand for orthopedic and dental implants will continue to grow, and for these applications, titanium and its alloys have been used extensively. While these implants have achieved high success rates, two major complications may be encountered: the lack of bone tissue integration and implant-centered infection. The surface of the implant, through its interactions with proteins, bacteria and tissue cells, plays a determining role in the success or failure of the implant. Ideally, to enhance the success of implants, their surfaces should inhibit bacterial colonization and concomitantly promote osteoblast functions. In this article, we discuss strategies for tailoring implant surfaces by exploiting the differences in the response of bacteria and osteoblasts to proteins and surface structures. Nevertheless, limitations still exist in the quest for an ideal implant surface. Further advances in this field will require concurrent development in surface modification techniques and a better understanding of the complex and highly inter-related events occurring at the implant surface after implantation.
Topics: Bacterial Adhesion; Cell Communication; Osteoblasts; Prostheses and Implants; Surface Properties; Titanium
PubMed: 22257725
DOI: 10.1016/j.biomaterials.2012.01.018