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Journal of Bone and Mineral Metabolism Jan 2021In bone tissue, bone resorption by osteoclasts and bone formation by osteoblasts are repeated continuously. Osteoclasts are multinucleated cells that derive from... (Review)
Review
INTRODUCTION
In bone tissue, bone resorption by osteoclasts and bone formation by osteoblasts are repeated continuously. Osteoclasts are multinucleated cells that derive from monocyte-/macrophage-lineage cells and resorb bone. In contrast, osteoblasts mediate osteoclastogenesis by expressing receptor activator of nuclear factor-kappa B ligand (RANKL), which is expressed as a membrane-associated cytokine. Osteoprotegerin (OPG) is a soluble RANKL decoy receptor that is predominantly produced by osteoblasts and which prevents osteoclast formation and osteoclastic bone resorption by inhibiting the RANKL-RANKL receptor interaction.
MATERIALS AND METHODS
In this review, we would like to summarize our experimental results on signal transduction that regulates the expression of RANKL and OPG.
RESULTS
Using OPG gene-deficient mice, we have demonstrated that OPG and sclerostin produced by osteocytes play an important role in the maintenance of cortical and alveolar bone. In addition, it was shown that osteoclast-derived leukemia inhibitory factor (LIF) reduces the expression of sclerostin in osteocytes and promotes bone formation. WP9QY (W9) is a peptide that was designed to be structurally similar to one of the cysteine-rich TNF-receptortype-I domains. Addition of the W9 peptide to bone marrow culture simultaneously inhibited osteoclast differentiation and stimulated osteoblastic cell proliferation. An anti-sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) antibody inhibited multinucleated osteoclast formation induced by RANKL and macrophage colony-stimulating factor (M-CSF). Pit-forming activity of osteoclasts was also inhibited by the anti-Siglec-15 antibody. In addition, anti-Siglec-15 antibody treatment stimulated the appearance of osteoblasts in cultures of mouse bone marrow cells in the presence of RANKL and M-CSF.
CONCLUSIONS
Bone mass loss depends on the RANK-RANKL-OPG system, which is a major regulatory system of osteoclast differentiation induction, activation, and survival.
Topics: Animals; Cell Differentiation; Humans; Osteoclasts; Osteogenesis; Osteoprotegerin; RANK Ligand; Signal Transduction
PubMed: 33079279
DOI: 10.1007/s00774-020-01162-6 -
Journal of Cellular Physiology Jul 2019Established RAW264.7 cell lines for osteoclastic differentiation has been widely engaged in bone homeostasis research, however, the efficacy of RANKL independently...
Established RAW264.7 cell lines for osteoclastic differentiation has been widely engaged in bone homeostasis research, however, the efficacy of RANKL independently stimulating has rarely been defined, because protocols were usually developed and modified by various laboratories. Otherwise, problematic issues are also lie in the cell's seeding density, RANKL stimulating time point, and distinguishing osteoclastogenesis ability of RANKL-treated RAW264.7 cells. Therefore, in the current study, we examined the efficacy of various concentrations of RANKL-treated RAW264.7 for its osteoclastic differentiation with or without pretreated other costimulators such as: LPS and/or M-CSF. The oteoclastogenesis ability of RANKL-treated RAW264.7 cells was demonstrated by bone resorption pit, F-actin, and osteoclastogenesis specific marker studies. Besides that, through tartrate-resistant acid phosphatase (TRAP) staining, we clarified to start the treatment with 30 ng/ml RANKL at 12 hr after seeded RAW264.7 with the density of 6.25 × 10 cells/cm manifested an significantly increased number of multinucleated osteoclastic cells. Overall, our results establishing an optimal method for RANKL independently inducing RAW 264.7 cell osteoclastic differentiation, which could efficiently generate osteoclasts in vitro for significant advances in our understanding of bone biology.
Topics: Animals; Bone Resorption; Bone and Bones; Cell Differentiation; Macrophage Colony-Stimulating Factor; Macrophages; Membrane Glycoproteins; Mice; Osteoclasts; Osteogenesis; RANK Ligand; RAW 264.7 Cells; Receptor Activator of Nuclear Factor-kappa B
PubMed: 30515780
DOI: 10.1002/jcp.27852 -
Critical Reviews in Oral Biology and... 1991The osteoclast is the primary bone resorbing cell. It is a highly specialized multinucleated cell whose primary function is to help in the control of calcium... (Review)
Review
The osteoclast is the primary bone resorbing cell. It is a highly specialized multinucleated cell whose primary function is to help in the control of calcium homeostasis. The osteoclast has been very difficult to study because of its relative inaccessability, low numbers, and fragility when isolated from bone. Recently, techniques have been developed to study the cell biology of the osteoclast that have expanded our ability to understand the biological and functional properties of osteoclasts. In this article, studies on the origin of the osteoclast are reviewed and the differentiation markers that are used to detect cells in the osteoclast lineage are discussed. Factors that affect osteoclast differentiation are presented and model systems currently in use for studying osteoclast differentiation are evaluated for their relative strengths and weaknesses. In addition, osteoclast differentiation during tooth eruption and root resorption and the effects of bone matrix elements on osteoclast differentiation are reviewed.
Topics: Cell Differentiation; Humans; Osteoclasts
PubMed: 1892993
DOI: 10.1177/10454411910020030601 -
Histochemistry and Cell Biology Apr 2018The bone is an essential organ for locomotion and protection of the body, as well as hematopoiesis and mineral homeostasis. In order to exert these functions throughout... (Review)
Review
The bone is an essential organ for locomotion and protection of the body, as well as hematopoiesis and mineral homeostasis. In order to exert these functions throughout life, bone tissue undergoes a repeating cycle of osteoclastic bone resorption and osteoblastic bone formation. The osteoclast is a large, multinucleated cell that is differentiated from monocyte/macrophage lineage cells by macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL). RANKL transduces its signal through the signaling receptor, RANK. RANKL/RANK signaling activates NFATc1, the master regulator of osteoclastogenesis, to induce osteoclastogenic gene expression. Many types of cells express RANKL to support osteoclastogenesis depending on the biological context and the dysregulation of RANKL signaling leads to bone diseases such as osteoporosis and osteopetrosis. This review outlines the findings on osteoclast and RANKL/RANK signaling that have accumulated to date.
Topics: Animals; Humans; Osteoclasts; RANK Ligand; Signal Transduction
PubMed: 29392395
DOI: 10.1007/s00418-018-1636-2 -
Archives of Biochemistry and Biophysics Sep 2014Much has been written recently on osteoclast biology, but this cell type still astonishes scientists with its multifaceted functions and unique properties. The last... (Review)
Review
Much has been written recently on osteoclast biology, but this cell type still astonishes scientists with its multifaceted functions and unique properties. The last three decades have seen a change in thinking about the osteoclast, from a cell with a single function, which just destroys the tissue it belongs to, to an "orchestrator" implicated in the concerted regulation of bone turnover. Osteoclasts have unique morphological features, organelle distribution and plasma membrane domain organization. They require polarization to cause extracellular bone breakdown and release of the digested bone matrix products into the circulation. Osteoclasts contribute to the control of skeletal growth and renewal. Alongside other organs, including kidney, gut, thyroid and parathyroid glands, they also affect calcemia and phosphatemia. Osteoclasts are very sensitive to pro-inflammatory stimuli, and studies in the '00s ascertained their tight link with the immune system, bringing about the question why bone needs a cell regulated by the immune system to remove the extracellular matrix components. Recently, osteoclasts have been demonstrated to contribute to the hematopoietic stem cell niche, controlling local calcium concentration and regulating the turnover of factors essential for hematopoietic stem cell mobilization. Finally, osteoclasts are important regulators of osteoblast activity and angiogenesis, both by releasing factors stored in the bone matrix, and secreting "clastokines" that regulate the activity of neighboring cells. All these facets will be discussed in this review article, with the aim of underscoring The Great Beauty of the osteoclast.
Topics: Animals; Bone Resorption; Calcium; Homeostasis; Humans; Immunity; Osteoclasts; Phosphates
PubMed: 24976175
DOI: 10.1016/j.abb.2014.06.017 -
Frontiers in Bioscience : a Journal and... Jan 2007Osteoclasts, the bone resorbing cells, play a key role both in normal bone remodeling and in the skeletal osteopenia of arthritis, osteoporosis, periodontal disease and... (Review)
Review
Osteoclasts, the bone resorbing cells, play a key role both in normal bone remodeling and in the skeletal osteopenia of arthritis, osteoporosis, periodontal disease and certain malignancies. Osteoclast cellular commitment, differentiation and function depend upon the establishment of specific patterns of gene expression achieved through networks of transcription factors activated by osteoclastogenic cytokines. This review is an updated look at the various transcription factors and cytokines that have been demonstrated to play critical roles in osteoclast differentiation and function, along with their known animal models, such as: PU.1, Mcsf, RANKL, NF-kappaB, AP-1, NFATc1, Mitf, Myc, and Src. Further studies on these transcription factors and cytokines will not only expand our basic understanding of the molecular mechanisms of osteoclast differentiation, but will also aid our ability to develop therapeutic means of intervention in osteoclast-related diseases.
Topics: Animals; Cell Differentiation; Cell Lineage; Cytokines; Gene Expression Regulation; Humans; Osteoclasts; RANK Ligand; Signal Transduction; Transcription Factors
PubMed: 17127260
DOI: 10.2741/2252 -
Seminars in Cell & Developmental Biology Apr 2021Osteoclasts, the multinucleated cells responsible for bone resorption, have an enormous destructive power which demands to be kept under tight control. Accordingly, the... (Review)
Review
Osteoclasts, the multinucleated cells responsible for bone resorption, have an enormous destructive power which demands to be kept under tight control. Accordingly, the identification of molecular signals directing osteoclastogenesis and switching on their resorptive activity have received much attention. Mandatory factors were identified, but a very essential aspect of the control mechanism of osteoclastic resorption, i.e. its spatial control, remains poorly understood. Under physiological conditions, multinucleated osteoclasts are only detected on the bone surface, while their mono-nucleated precursors are only in the bone marrow. How are pre-osteoclasts targeted to the bone surface? How is their progressive differentiation coordinated with their approach to the bone surface sites to be resorbed, which is where they finally fuse? Here we review the information on the bone marrow distribution of differentiating pre-osteoclasts relative to the position of the mandatory factors for their differentiation as well as relative to physical entities that may affect their access to the remodelling sites. This info allows recognizing an "osteoclastogenesis route" through the bone marrow and leading to the coincident fusion/resorption site - but also points to what still remains to be clarified regarding this route and regarding the restriction of fusion at the resorption site. Finally, we discuss the mechanism responsible for the start of resorption and its spatial extension. This review underscores that fully understanding the control of bone resorption requires to consider it in both space and time - which demands taking into account the context of bone tissue.
Topics: Bone Marrow Cells; Bone Resorption; Cell Communication; Cell Differentiation; Humans; Osteoclasts; Osteogenesis; Surface Properties
PubMed: 32563679
DOI: 10.1016/j.semcdb.2020.05.016 -
Journal of Cellular Biochemistry Aug 2016The accepted function of the bone resorbing cell, osteoclast, has been linked to bone remodeling and pathological osteolysis. Emerging evidence points to novel functions... (Review)
Review
The accepted function of the bone resorbing cell, osteoclast, has been linked to bone remodeling and pathological osteolysis. Emerging evidence points to novel functions of osteoclasts in controlling bone formation and angiogenesis. Thus, while the concept of a "clastokine" with the potential to regulate osteogenesis during remodeling did not come as a surprise, new evidence provided unique insight into the mechanisms underlying osteoclastic control of bone formation. The question still remains as to whether osteoclast precursors or a unique trap positive mononuclear cell, can govern any aspect of bone formation. The novel paradigm eloquently proposed by leaders in the field brings together the concept of clastokines and osteoclast precursor-mediated bone formation, potentially though enhanced angiogenesis. These fascinating advances in osteoclast biology have motivated this short review, in which we discuss these new roles of osteoclasts. J. Cell. Biochem. 117: 1753-1756, 2016. © 2016 Wiley Periodicals, Inc.
Topics: Animals; Humans; Neovascularization, Physiologic; Osteoclasts; Osteogenesis; Osteolysis
PubMed: 27019318
DOI: 10.1002/jcb.25560 -
Fitoterapia Apr 2020Natural products have been investigated as potential candidates of novel therapeutics and play a crucial role in advanced medicinal drugs. Natural resources, including... (Review)
Review
Natural products have been investigated as potential candidates of novel therapeutics and play a crucial role in advanced medicinal drugs. Natural resources, including local medicinal plants (especially folk medicinal plants), animals, bacteria, and fungi have been used for more than a century, and are precious gifts from nature, providing potential medicines with high safety. Osteoclast-related diseases, such as osteoporosis, rheumatoid arthritis, Paget's disease, osteoclastoma, and periprosthetic osteolysis, are currently the most common reasons for bone inflammation, pain and fractures, resulting in low quality of life. However, the curative effects of current therapeutic drugs for these osteoclast-related diseases are limited, and long-term treatment is needed. Further, in severe cases, surgical treatments are necessary, which may cause unaffordable expenses and subsequent influences such as neuralgia, mental stress, and even development of cancer. Thus, safer inhibitors and potential drugs with enhanced curative effects and quick relief are needed to treat patients with osteoclast diseases. This review aims to introduce the main osteoclast-related diseases and some of the recently developed naturally sourced inhibitors against osteoclastogenesis, also it is desired to attract people's attention on using widely available natural resources for the evolution of new types of osteoclast inhibitors with minimal or no side-effects upon long-term treatments.
Topics: Biological Products; Bone Diseases; Cell Proliferation; Humans; Osteoclasts; Phytotherapy
PubMed: 31954740
DOI: 10.1016/j.fitote.2020.104482 -
BioMed Research International 2015Bone tissue is continuously remodeled through the concerted actions of bone cells, which include bone resorption by osteoclasts and bone formation by osteoblasts,... (Review)
Review
Bone tissue is continuously remodeled through the concerted actions of bone cells, which include bone resorption by osteoclasts and bone formation by osteoblasts, whereas osteocytes act as mechanosensors and orchestrators of the bone remodeling process. This process is under the control of local (e.g., growth factors and cytokines) and systemic (e.g., calcitonin and estrogens) factors that all together contribute for bone homeostasis. An imbalance between bone resorption and formation can result in bone diseases including osteoporosis. Recently, it has been recognized that, during bone remodeling, there are an intricate communication among bone cells. For instance, the coupling from bone resorption to bone formation is achieved by interaction between osteoclasts and osteoblasts. Moreover, osteocytes produce factors that influence osteoblast and osteoclast activities, whereas osteocyte apoptosis is followed by osteoclastic bone resorption. The increasing knowledge about the structure and functions of bone cells contributed to a better understanding of bone biology. It has been suggested that there is a complex communication between bone cells and other organs, indicating the dynamic nature of bone tissue. In this review, we discuss the current data about the structure and functions of bone cells and the factors that influence bone remodeling.
Topics: Animals; Bone Remodeling; Bone and Bones; Calcification, Physiologic; Cell Communication; Humans; Models, Biological; Osteoblasts; Osteoclasts; Structure-Activity Relationship
PubMed: 26247020
DOI: 10.1155/2015/421746