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Arthritis Research & Therapy Jul 2011Bone remodeling in physiological and pathological conditions represents a balance between bone resorption mediated by osteoclasts and bone formation by osteoblasts. Bone... (Review)
Review
Bone remodeling in physiological and pathological conditions represents a balance between bone resorption mediated by osteoclasts and bone formation by osteoblasts. Bone resorption is tightly and dynamically regulated by multiple mediators, including cytokines that act directly on osteoclasts and their precursors, or indirectly by modulating osteoblast lineage cells that in turn regulate osteoclast differentiation. The critical role of cytokines in inducing and promoting osteoclast differentiation, function and survival is covered by the accompanying review by Zwerina and colleagues. Recently, it has become clear that negative regulation of osteoclastogenesis and bone resorption by inflammatory factors and cytokines, downstream signaling pathways, and a newly described network of transcriptional repressors plays a key role in bone homeostasis by fine tuning bone remodeling and restraining excessive bone resorption in inflammatory settings. In this review we discuss negative regulators of osteoclastogenesis and mechanisms by which these factors suppress bone resorption.
Topics: Animals; Bone Resorption; Cell Differentiation; Cytokines; Humans; Osteoclasts; Signal Transduction; Transcription, Genetic
PubMed: 21861861
DOI: 10.1186/ar3379 -
International Journal of Molecular... May 2019Alterations in the process of mechanotransduction have been implicated in the pathogenesis of several diseases such as genetic diseases, osteoporosis, cardiovascular... (Review)
Review
Alterations in the process of mechanotransduction have been implicated in the pathogenesis of several diseases such as genetic diseases, osteoporosis, cardiovascular anomalies, and cancer. Several studies over the past twenty years have demonstrated that polycystins (polycystin-1, PC1; and polycystin-2, PC2) respond to changes of extracellular mechanical cues, and mediate pathogenic mechanotransduction and cyst formation in kidney cells. However, recent reports reveal the emergence of polycystins as key proteins that facilitate the transduction of mechano-induced signals in various clinical entities besides polycystic kidney disease, such as cancer, cardiovascular defects, bone loss, and deformations, as well as inflammatory processes like psoriasis. Herewith, we discuss data from recent studies that establish this role with potential clinical utility.
Topics: Animals; Bone Resorption; Cardiomyopathies; Humans; Mechanotransduction, Cellular; Neoplasms; Psoriasis; TRPP Cation Channels
PubMed: 31052533
DOI: 10.3390/ijms20092182 -
Bone Mar 2016The impact of bariatric surgery on cardiovascular and diabetic complications associated with an improvement in survival has overshadowed the adverse skeletal health and... (Review)
Review
The impact of bariatric surgery on cardiovascular and diabetic complications associated with an improvement in survival has overshadowed the adverse skeletal health and development of kidney stone disease in this population. All longitudinal based studies in the literature reporting the incidence of bone fractures or kidney stones following bariatric surgery were reviewed. Moreover, all publications over the past decade which assessed changes in bone mineral density and bone quality, or explored underlying pathophysiologic mechanisms of bone and kidney stone disease were carefully reviewed. This review provides sufficient data to support that osteoporotic fractures and kidney stone disease are associated with Roux-en-Y gastric bypass surgery. However, due to the limited data available to date, no definitive conclusion could yet be drawn whether sleeve gastrectomy or adjustable gastric banding is associated with bone fractures and kidney stones. Bariatric surgery has emerged as the most effective and sustained treatment for weight reduction. This treatment modality has been recognized to diminish the risk of cardiovascular morbidity and mortality and ameliorate diabetes mellitus complications. The derangement in mineral metabolism has emerged as a major complication following bariatric surgery.
Topics: Bariatric Surgery; Bone Density; Bone Resorption; Bone and Bones; Fractures, Bone; Humans; Nephrolithiasis
PubMed: 26679435
DOI: 10.1016/j.bone.2015.12.001 -
Seminars in Cell & Developmental Biology Jan 2016Remodeling of bone is a continuous process that occurs throughout life. Under normal physiologic conditions, bone-resorbing osteoclasts and bone-forming osteoblasts are... (Review)
Review
Remodeling of bone is a continuous process that occurs throughout life. Under normal physiologic conditions, bone-resorbing osteoclasts and bone-forming osteoblasts are tightly coupled and regulated to ensure proper balance, such that there is no net change in bone mass. However, inflammation perturbs normal bone homeostasis. The impact of inflammation on bone is dependent upon the anatomic site affected, cell types, factors and cytokines present in the local microenvironment, and local mechanical forces. Cytokines are central to the pathogenesis of inflammation-induced bone loss and contribute to the uncoupling of osteoclast-mediated bone resorption and osteoblast-mediated bone formation, thereby disrupting normal remodeling. In this review, we will discuss the effects of cytokines on bone in two settings, rheumatoid arthritis and spondyloarthritis, a disease category that includes ankylosing spondylitis, psoriatic arthritis, reactive arthritis, inflammatory bowel disease, and juvenile onset spondyloarthropathy. The outcome for bone in these disease settings is quite different, and an understanding of the pathogenic mechanisms leading to the net impact on bone has been essential in developing new therapeutic approaches to bone health in these diseases.
Topics: Animals; Arthritis, Rheumatoid; Bone Resorption; Cytokines; Humans; Inflammation Mediators; Osteoblasts; Osteoclasts; Signal Transduction
PubMed: 26481971
DOI: 10.1016/j.semcdb.2015.10.013 -
International Journal of Molecular... Feb 2022Bone is a mineralized and elastic connective tissue that provides fundamental functions in the human body, including mechanical support to the muscles and joints,... (Review)
Review
Bone is a mineralized and elastic connective tissue that provides fundamental functions in the human body, including mechanical support to the muscles and joints, protection of vital organs and storage of minerals. Bone is a metabolically active organ that undergoes continuous remodeling processes to maintain its architecture, shape, and function throughout life. One of the most important medical discoveries of recent decades has been that the immune system is involved in bone remodeling. Indeed, chronic inflammation has been recognized as the most significant factor influencing bone homeostasis, causing a shift in the bone remodeling process toward pathological bone resorption. Bone osteolytic diseases typified by excessive bone resorption account for one of the greatest causes of disability worldwide, with significant economic and public health burdens. From this perspective, we discuss the recent findings and discoveries highlighting the cellular and molecular mechanisms that regulate this process in the bone microenvironment, in addition to the current therapeutic strategies for the treatment of osteolytic bone diseases.
Topics: Bone Resorption; Humans; Inflammation; Osteoclasts
PubMed: 35163708
DOI: 10.3390/ijms23031786 -
Biomolecules Sep 2020Autophagy is an evolutionary conserved and highly regulated recycling process of cellular wastes. Having a housekeeping role, autophagy through the digestion of domestic... (Review)
Review
Autophagy is an evolutionary conserved and highly regulated recycling process of cellular wastes. Having a housekeeping role, autophagy through the digestion of domestic cytosolic organelles, proteins, macromolecules, and pathogens, eliminates unnecessary materials and provides nutrients and energy for cell survival and maintenance. The critical role of autophagy and autophagy-related proteins in osteoclast differentiation, bone resorption, and maintenance of bone homeostasis has previously been reported. Increasing evidence reveals that autophagy dysregulation leads to alteration of osteoclast function and enhanced bone loss, which is associated with the onset and progression of osteoporosis. In this review, we briefly consolidate the current state-of-the-art technology regarding the role of autophagy in osteoclast function in both physiologic and pathologic conditions to have a more general view on this issue.
Topics: Autophagy; Autophagy-Related Proteins; Bone Resorption; Cell Differentiation; Cell Survival; Humans; Osteoclasts; Osteoporosis
PubMed: 33008140
DOI: 10.3390/biom10101398 -
Expert Review of Clinical Pharmacology Sep 2011Inflammatory arthritis is a group of autoimmune diseases characterized by chronic inflammation of the joints. Rheumatoid arthritis, the most common form of arthritis, is... (Review)
Review
Inflammatory arthritis is a group of autoimmune diseases characterized by chronic inflammation of the joints. Rheumatoid arthritis, the most common form of arthritis, is associated with local joint destruction and systemic bone loss. Osteoclasts, the only cells of the body able to resorbe bone, are key players in these two types of bone loss. Bisphosphonates are analogs of pyrophosphate that inhibit osteoclast action and bone resorption. They are indicated in pathology associated with excess resorption. Besides their effect on bone they also exhibit extra-osseous properties, acting on tumor cells, inflammation and angiogenesis. As a result, they have been trialed in the context of arthritis. It is now clear that they do not have any significant direct effect on disease activity or pain. If their indication in the prevention of glucocorticoid-induced osteoporosis is clear, any beneficial effects on bone erosions are still controversial but interesting preliminary results warrant further investigations.
Topics: Animals; Bone Resorption; Clinical Trials as Topic; Diphosphonates; Humans; Osteoarthritis; Osteoclasts
PubMed: 22220307
DOI: 10.1586/ecp.11.40 -
Biomolecules Aug 2018The aim of this mini-review is to discuss the role of calcium in the process of cytokine-mediated bone resorption in an effort to understand the role circulating calcium... (Review)
Review
The aim of this mini-review is to discuss the role of calcium in the process of cytokine-mediated bone resorption in an effort to understand the role circulating calcium may play in the resorption of bone. The liberation of calcium and possibly phosphorus and magnesium by bone resorption may sustain and intensify the inflammatory response. We used a burn injury setting in humans and a burn injury model in animals in order to examine the effects on the bone of the systemic inflammatory response and identified the parathyroid calcium-sensing receptor as the mediator of increasing bone resorption, hence higher interleukin (IL)-1 production, and decreasing bone resorption, hence the lowering of circulating ionized calcium concentration. Thus, extracellular calcium, by means of the parathyroid calcium-sensing receptor, is able to modulate inflammation-mediated resorption.
Topics: Animals; Bone Resorption; Calcium; Humans; Inflammation; Interleukin-1
PubMed: 30071694
DOI: 10.3390/biom8030069 -
The Keio Journal of Medicine Sep 2005Chronic inflammatory bone diseases, such as rheumatoid arthritis, periodontal disease and aseptic periprosthetic osteolysis, are characterized by bone loss around... (Review)
Review
Chronic inflammatory bone diseases, such as rheumatoid arthritis, periodontal disease and aseptic periprosthetic osteolysis, are characterized by bone loss around affected joints and teeth caused by increased osteoclastic bone resorption. This resorption is mediated largely by the increased local production of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNFa). These cytokines may induce resorption indirectly by affecting the production of the essential osteoclast differentiation factor, receptor activator of NF-kB ligand, and/or its soluble decoy receptor, osteoprotegerin, by osteoblast/stromal cells or directly by enhancing proliferation and/or activity of cells in the osteoclast lineage. The importance of TNFa in the pathogenesis of various forms of bone loss is supported by both experimental and clinical evidence. However, TNFa is not absolutely required for osteoclastogenesis, erosive arthritis, or osteolysis, as all these events could occur in the absence of TNFa and whether TNFa promotes osteoclast formation independently of RANK signaling is still a topic of debate. Here we review our current understanding of the mechanisms whereby TNFa increases osteoclastogenesis in vitro and in vivo.
Topics: Animals; Arthritis, Experimental; Bone Resorption; Cytokines; Humans; Mice; Osteoclasts; Tumor Necrosis Factor-alpha
PubMed: 16237274
DOI: 10.2302/kjm.54.127 -
Nature Reviews. Endocrinology Sep 2016Osteoporosis develops when the rate of osteoclastic bone breakdown (resorption) exceeds that of osteoblastic bone formation, which leads to loss of BMD and deterioration... (Review)
Review
Osteoporosis develops when the rate of osteoclastic bone breakdown (resorption) exceeds that of osteoblastic bone formation, which leads to loss of BMD and deterioration of bone structure and strength. Osteoporosis increases the risk of fragility fractures, a cause of substantial morbidity and mortality, especially in elderly patients. This imbalance between bone formation and bone resorption is brought about by natural ageing processes, but is frequently exacerbated by a number of pathological conditions. Of importance to the aetiology of osteoporosis are findings over the past two decades attesting to a deep integration of the skeletal system with the immune system (the immuno-skeletal interface (ISI)). Although protective of the skeleton under physiological conditions, the ISI might contribute to bone destruction in a growing number of pathophysiological states. Although numerous research groups have investigated how the immune system affects basal and pathological osteoclastic bone resorption, recent findings suggest that the reach of the adaptive immune response extends to the regulation of osteoblastic bone formation. This Review examines the evolution of the field of osteoimmunology and how advances in our understanding of the ISI might lead to novel approaches to prevent and treat bone loss, and avert fractures.
Topics: Animals; Bone Density; Bone Diseases, Metabolic; Bone Remodeling; Bone Resorption; Fractures, Bone; Humans; Immune System; Osteoporosis
PubMed: 27312863
DOI: 10.1038/nrendo.2016.91