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Cells Sep 2020Bone remodeling is tightly regulated by a cross-talk between bone-forming osteoblasts and bone-resorbing osteoclasts. Osteoblasts and osteoclasts communicate with each... (Review)
Review
Bone remodeling is tightly regulated by a cross-talk between bone-forming osteoblasts and bone-resorbing osteoclasts. Osteoblasts and osteoclasts communicate with each other to regulate cellular behavior, survival and differentiation through direct cell-to-cell contact or through secretory proteins. A direct interaction between osteoblasts and osteoclasts allows bidirectional transduction of activation signals through EFNB2-EPHB4, FASL-FAS or SEMA3A-NRP1, regulating differentiation and survival of osteoblasts or osteoclasts. Alternatively, osteoblasts produce a range of different secretory molecules, including M-CSF, RANKL/OPG, WNT5A, and WNT16, that promote or suppress osteoclast differentiation and development. Osteoclasts also influence osteoblast formation and differentiation through secretion of soluble factors, including S1P, SEMA4D, CTHRC1 and C3. Here we review the current knowledge regarding membrane bound- and soluble factors governing cross-talk between osteoblasts and osteoclasts.
Topics: Bone Remodeling; Bone and Bones; Cell Communication; Cell Differentiation; Homeostasis; Humans; Osteoblasts; Osteoclasts; Signal Transduction
PubMed: 32927921
DOI: 10.3390/cells9092073 -
Connective Tissue Research Mar 2018Bone homeostasis depends on the resorption of bones by osteoclasts and formation of bones by the osteoblasts. Imbalance of this tightly coupled process can cause... (Review)
Review
Bone homeostasis depends on the resorption of bones by osteoclasts and formation of bones by the osteoblasts. Imbalance of this tightly coupled process can cause diseases such as osteoporosis. Thus, the mechanisms that regulate communication between osteoclasts and osteoblasts are critical to bone cell biology. It has been shown that osteoblasts and osteoclasts can communicate with each other through direct cell-cell contact, cytokines, and extracellular matrix interaction. Osteoblasts can affect osteoclast formation, differentiation, or apoptosis through several pathways, such as OPG/RANKL/RANK, RANKL/LGR4/RANK, Ephrin2/ephB4, and Fas/FasL pathways. Conversely, osteoclasts also influence formation of bones by osteoblasts via the d2 isoform of the vacuolar (H+) ATPase (v-ATPase) V0 domain (Atp6v0d2), complement component 3a, semaphorin 4D or microRNAs. In addition, cytokines released from the resorbed bone matrix, such as TGF-β and IGF-1, also affect the activity of osteoblasts. Drugs could be developed by enhancing or restricting some of these interactions. Several reviews have been performed on the osteoblast-osteoclast communication. However, few reviews have shown the research advances in the recent years. In this review, we summarized the current knowledge on osteoblast-osteoclast communication.
Topics: Animals; Apoptosis; Cell Communication; Cell Differentiation; Humans; Osteoblasts; Osteoclasts; Osteogenesis; Signal Transduction
PubMed: 28324674
DOI: 10.1080/03008207.2017.1290085 -
Annual Review of Pathology Jan 2023Osteoclasts are multinucleated cells with the unique ability to resorb bone matrix. Excessive production or activation of osteoclasts leads to skeletal pathologies that... (Review)
Review
Osteoclasts are multinucleated cells with the unique ability to resorb bone matrix. Excessive production or activation of osteoclasts leads to skeletal pathologies that affect a significant portion of the population. Although therapies that effectively target osteoclasts have been developed, they are associated with sometimes severe side effects, and a fuller understanding of osteoclast biology may lead to more specific treatments. Along those lines, a rich body of work has defined essential signaling pathways required for osteoclast formation, function, and survival. Nonetheless, recent studies have cast new light on long-held views regarding the origin of these cells during development and homeostasis, their life span, and the cellular sources of factors that drive their production and activity during homeostasis and disease. In this review, we discuss these new findings in the context of existing work and highlight areas of ongoing and future investigation.
Topics: Humans; Osteoclasts; Bone Resorption; Signal Transduction; Cell Differentiation
PubMed: 36207010
DOI: 10.1146/annurev-pathmechdis-031521-040919 -
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 -
Cells Dec 2021Increased osteoclast (OC) differentiation and activity is the critical event that results in bone loss and joint destruction in common pathological bone conditions, such... (Review)
Review
Increased osteoclast (OC) differentiation and activity is the critical event that results in bone loss and joint destruction in common pathological bone conditions, such as osteoporosis and rheumatoid arthritis (RA). RANKL and its decoy receptor, osteoprotegerin (OPG), control OC differentiation and activity. However, there is a specific concern of a rebound effect of denosumab discontinuation in treating osteoporosis. TNFα can induce OC differentiation that is independent of the RANKL/RANK system. In this review, we discuss the factors that negatively and positively regulate TNFα induction of OC formation, and the mechanisms involved to inform the design of new anti-resorptive agents for the treatment of bone conditions with enhanced OC formation. Similar to, and being independent of, RANKL, TNFα recruits TNF receptor-associated factors (TRAFs) to sequentially activate transcriptional factors NF-κB p50 and p52, followed by c-Fos, and then NFATc1 to induce OC differentiation. However, induction of OC formation by TNFα alone is very limited, since it also induces many inhibitory proteins, such as TRAF3, p100, IRF8, and RBP-j. TNFα induction of OC differentiation is, however, versatile, and Interleukin-1 or TGFβ1 can enhance TNFα-induced OC formation through a mechanism which is independent of RANKL, TRAF6, and/or NF-κB. However, TNFα polarized macrophages also produce anabolic factors, including insulin such as 6 peptide and Jagged1, to slow down bone loss in the pathological conditions. Thus, the development of novel approaches targeting TNFα signaling should focus on its downstream molecules that do not affect its anabolic effect.
Topics: Animals; Arthritis, Rheumatoid; Cell Differentiation; Humans; Osteoclasts; Osteoporosis; Signal Transduction; Tumor Necrosis Factor-alpha
PubMed: 35011694
DOI: 10.3390/cells11010132 -
Frontiers in Immunology 2021Osteoimmunity is involved in regulating the balance of bone remodeling and resorption, and is essential for maintaining normal bone morphology. The interaction between... (Review)
Review
Osteoimmunity is involved in regulating the balance of bone remodeling and resorption, and is essential for maintaining normal bone morphology. The interaction between immune cells and osteoclasts in the bone marrow or joint cavity is the basis of osteoimmunity, in which the macrophage-osteoclast axis plays a vital role. Monocytes or tissue-specific macrophages (macrophages resident in tissues) are an important origin of osteoclasts in inflammatory and immune environment. Although there are many reports on macrophages and osteoclasts, there is still a lack of systematic reviews on the macrophage-osteoclast axis in osteoimmunity. Elucidating the role of the macrophage-osteoclast axis in osteoimmunity is of great significance for the research or treatment of bone damage caused by inflammation and immune diseases. In this article, we introduced in detail the concept of osteoimmunity and the mechanism and regulators of the differentiation of macrophages into osteoclasts. Furthermore, we described the role of the macrophage-osteoclast axis in typical bone damage caused by inflammation and immune diseases. These provide a clear knowledge framework for studying macrophages and osteoclasts in inflammatory and immune environments. And targeting the macrophage-osteoclast axis may be an effective strategy to treat bone damage caused by inflammation and immune diseases.
Topics: Animals; Arthritis, Rheumatoid; Bone Remodeling; Bone Resorption; Bone and Bones; Cell Differentiation; Humans; Macrophages; Osteoclasts
PubMed: 33868316
DOI: 10.3389/fimmu.2021.664871 -
Genesis (New York, N.Y. : 2000) Sep 2022Osteoclasts are large multinucleated cells from hematopoietic origin and are responsible for bone resorption. A balance between osteoclastic bone resorption and... (Review)
Review
Osteoclasts are large multinucleated cells from hematopoietic origin and are responsible for bone resorption. A balance between osteoclastic bone resorption and osteoblastic bone formation is critical to maintain bone homeostasis. The alveolar bone, also called the alveolar process, is the part of the jawbone that holds the teeth and supports oral functions. It differs from other skeletal bones in several aspects: its embryonic cellular origin, the form of ossification, and the presence of teeth and periodontal tissues; hence, understanding the unique characteristic of the alveolar bone remodeling is important to maintain oral homeostasis. Excessive osteoclastic bone resorption is one of the prominent features of bone diseases in the jaw such as periodontitis. Therefore, inhibiting osteoclast formation and bone resorptive process has been the target of therapeutic intervention. Understanding the mechanisms of osteoclastic bone resorption is critical for the effective treatment of bone diseases in the jaw. In this review, we discuss basic principles of alveolar bone remodeling with a specific focus on the osteoclastic bone resorptive process and its unique functions in the alveolar bone. Lastly, we provide perspectives on osteoclast-targeted therapies and regenerative approaches associated with bone diseases in the jaw.
Topics: Bone Remodeling; Bone Resorption; Bone and Bones; Humans; Osteoclasts; Osteogenesis
PubMed: 35757898
DOI: 10.1002/dvg.23490 -
Journal of Dental Research Oct 2013Osteoclasts are derived from mononuclear hematopoietic myeloid lineage cells, which are formed in the bone marrow and are attracted to the bloodstream by factors,... (Review)
Review
Osteoclasts are derived from mononuclear hematopoietic myeloid lineage cells, which are formed in the bone marrow and are attracted to the bloodstream by factors, including sphingsine-1 phosphate. These circulating precursors are attracted to bone surfaces undergoing resorption by chemokines and other factors expressed at these sites, where they fuse to form multinucleated bone-resorbing cells. All aspects of osteoclast formation and functions are regulated by macrophage-colony-stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL), cytokines essential for osteoclast formation and expressed by a variety of cell types, including osteoblast lineage cells. Since the discovery of RANKL in the mid-1990s, mouse genetic and molecular studies have revealed numerous signaling pathways activated by RANKL and M-CSF. More recent studies indicate that osteoclasts and their precursors regulate immune responses and osteoblast formation and functions by means of direct cell-cell contact through ligands and receptors, such as ephrins and Ephs, and semaphorins and plexins, and through expression of clastokines. There is also growing recognition that osteoclasts are immune cells with roles in immune responses beyond mediating the bone destruction that can accompany them. This article reviews recent advances in the understanding of the molecular mechanisms regulating osteoclast formation and functions and their interactions with other cells in normal and pathologic states.
Topics: Animals; Apoptosis; Bone Remodeling; Cell Communication; Cell Survival; Cytokines; Gene Expression Regulation; Humans; Macrophage Colony-Stimulating Factor; Osteoclasts; RANK Ligand; Signal Transduction
PubMed: 23906603
DOI: 10.1177/0022034513500306 -
Frontiers in Endocrinology 2021In recent decades, the mechanism underlying bone metabolic disorders based on energy metabolism has been heavily researched. Bone resorption by osteoclasts plays an... (Review)
Review
In recent decades, the mechanism underlying bone metabolic disorders based on energy metabolism has been heavily researched. Bone resorption by osteoclasts plays an important role in the occurrence and development of osteoporosis. However, the mechanism underlying the osteoclast energy metabolism disorder that interferes with bone homeostasis has not been determined. Bone resorption by osteoclasts is a process that consumes large amounts of adenosine triphosphate (ATP) produced by glycolysis and oxidative phosphorylation. In addition to glucose, fatty acids and amino acids can also be used as substrates to produce energy through oxidative phosphorylation. In this review, we summarize and analyze the energy-based phenotypic changes, epigenetic regulation, and coupling with systemic energy metabolism of osteoclasts during the development and progression of osteoporosis. At the same time, we propose a hypothesis, the compensatory recovery mechanism (involving the balance between osteoclast survival and functional activation), which may provide a new approach for the treatment of osteoporosis.
Topics: Animals; Energy Metabolism; Glucose; Glycolysis; Humans; Osteoclasts; Osteoporosis; Oxidative Phosphorylation
PubMed: 34054735
DOI: 10.3389/fendo.2021.675385 -
International Journal of Molecular... Jul 2019Reactive oxygen species (ROS) and free radicals are essential for transmission of cell signals and other physiological functions. However, excessive amounts of ROS can... (Review)
Review
Reactive oxygen species (ROS) and free radicals are essential for transmission of cell signals and other physiological functions. However, excessive amounts of ROS can cause cellular imbalance in reduction-oxidation reactions and disrupt normal biological functions, leading to oxidative stress, a condition known to be responsible for the development of several diseases. The biphasic role of ROS in cellular functions has been a target of pharmacological research. Osteoclasts are derived from hematopoietic progenitors in the bone and are essential for skeletal growth and remodeling, for the maintenance of bone architecture throughout lifespan, and for calcium metabolism during bone homeostasis. ROS, including superoxide ion (O) and hydrogen peroxide (HO), are important components that regulate the differentiation of osteoclasts. Under normal physiological conditions, ROS produced by osteoclasts stimulate and facilitate resorption of bone tissue. Thus, elucidating the effects of ROS during osteoclast differentiation is important when studying diseases associated with bone resorption such as osteoporosis. This review examines the effect of ROS on osteoclast differentiation and the efficacy of novel chemical compounds with therapeutic potential for osteoclast related diseases.
Topics: Animals; Biomarkers; Bone Remodeling; Bone Resorption; Cell Differentiation; Humans; Molecular Targeted Therapy; Osteoclasts; Osteogenesis; Oxidation-Reduction; Oxidative Stress; Reactive Oxygen Species; Signal Transduction
PubMed: 31336616
DOI: 10.3390/ijms20143576