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Biology Letters Feb 2018Activation of the immune system is associated with an increase in the breakdown of various peripheral tissues, including bone. Despite the widely appreciated role of... (Review)
Review
Activation of the immune system is associated with an increase in the breakdown of various peripheral tissues, including bone. Despite the widely appreciated role of inflammatory mediators in promoting bone resorption, the functional value behind this process is not completely understood. Recent advances in the field of immunometabolism have highlighted the metabolic reprogramming that takes place in activated immune cells. It is now believed that the breakdown of peripheral tissue provides metabolic substrates to fuel metabolic anabolism in activated immune cells. We argue that phosphate, liberated by bone resorption, plays an indispensable role in sustaining immune cell metabolism. The liberated phosphate is then incorporated into macromolecules such as nucleotides and phospholipids, and is also used for the phosphorylation of metabolites (e.g. glycolytic intermediates). In addition, magnesium, also liberated during the breakdown of bone, is an essential cofactor required by various metabolic enzymes which are upregulated in activated immune cells. Finally, calcium activates various additional molecules involved in immune cell migration. Taken together, these factors suggest a key role for bone resorption during infection.
Topics: Animals; Bone Resorption; Cell Movement; Cellular Reprogramming; Humans
PubMed: 29491030
DOI: 10.1098/rsbl.2017.0783 -
Operative Neurosurgery (Hagerstown, Md.) Apr 2021Following a decompressive craniectomy, the autologous bone flap is generally considered the reconstructive material of choice in pediatric patients. Replacement of the... (Review)
Review
Following a decompressive craniectomy, the autologous bone flap is generally considered the reconstructive material of choice in pediatric patients. Replacement of the original bone flap takes advantage of its natural biocompatibility and the associated low risk of rejection, as well as the potential to reintegrate with the adjacent bone and subsequently grow with the patient. However, despite these advantages and unlike adult patients, the replaced calvarial bone is more likely to undergo delayed bone resorption in pediatric patients, ultimately requiring revision surgery. In this review, we describe the materials that are currently available for pediatric cranioplasty, the advantages and disadvantages of autologous calvarial replacement, the incidence and classification of bone resorption, and the clinical risk factors for bone flap resorption that have been identified to date.
Topics: Adult; Bone Resorption; Child; Decompressive Craniectomy; Humans; Retrospective Studies; Skull; Surgical Flaps
PubMed: 33469664
DOI: 10.1093/ons/opaa452 -
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 -
Progress in Molecular Biology and... 2017Matrix metalloproteinases (MMPs) are the major protease family responsible for the cleavage of the matrisome (global composition of the extracellular matrix (ECM)... (Review)
Review
Matrix metalloproteinases (MMPs) are the major protease family responsible for the cleavage of the matrisome (global composition of the extracellular matrix (ECM) proteome) and proteins unrelated to the ECM, generating bioactive molecules. These proteins drive ECM remodeling, in association with tissue-specific and cell-anchored inhibitors (TIMPs and RECK, respectively). In the bone, the ECM mediates cell adhesion, mechanotransduction, nucleation of mineralization, and the immobilization of growth factors to protect them from damage or degradation. Since the first description of an MMP in bone tissue, many other MMPs have been identified, as well as their inhibitors. Numerous functions have been assigned to these proteins, including osteoblast/osteocyte differentiation, bone formation, solubilization of the osteoid during bone resorption, osteoclast recruitment and migration, and as a coupling factor in bone remodeling under physiological conditions. In turn, a number of pathologies, associated with imbalanced bone remodeling, arise mainly from MMP overexpression and abnormalities of the ECM, leading to bone osteolysis or bone formation. In this review, we will discuss the functions of MMPs and their inhibitors in bone cells, during bone remodeling, pathological bone resorption (osteoporosis and bone metastasis), bone repair/regeneration, and emergent roles in bone bioengineering.
Topics: Animals; Bone Regeneration; Bone Remodeling; Bone Resorption; Extracellular Matrix; Humans; Matrix Metalloproteinases; Wound Healing
PubMed: 28662823
DOI: 10.1016/bs.pmbts.2017.05.001 -
Frontiers in Endocrinology 2020TNF (Tumor necrosis factor) is a pleiotropic cytokine that plays an important role in immunity and inflammatory bone destruction. Homeostatic osteoclastogenesis is... (Review)
Review
TNF (Tumor necrosis factor) is a pleiotropic cytokine that plays an important role in immunity and inflammatory bone destruction. Homeostatic osteoclastogenesis is effectively induced by RANKL (Receptor activator of nuclear factor kappa-B ligand). In contrast, TNF often acts on cell types other than osteoclasts, or synergically with RANKL to indirectly promote osteoclastogenesis and bone resorption. TNF and RANKL are members of the TNF superfamily. However, the direct osteoclastogenic capacity of TNF is much weaker than that of RANKL. Recent studies have uncovered key intrinsic mechanisms by which TNF acts on osteoclast precursors to restrain osteoclastogenesis, including the mechanisms mediated by RBP-J signaling, RBP-J and ITAM (Immunoreceptor tyrosine-based activation motif) crosstalk, RBP-J mediated regulatory network, NF-B p100, IRF8, and Def6. Some of these mechanisms, such as RBP-J and its mediated regulatory network, uniquely and predominantly limit osteoclastogenesis mediated by TNF but not by RANKL. As a consequence, targeting RBP-J activities suppresses inflammatory bone destruction but does not significantly impact normal bone remodeling or inflammation. Hence, discovery of these intrinsic inhibitory mechanisms addresses why TNF has a weak osteoclastogenic potential, explains a significant difference between RANKL and TNF signaling, and provides potentially new or complementary therapeutic strategies to selectively treat inflammatory bone resorption, without undesirable effects on normal bone remodeling or immune response in disease settings.
Topics: Animals; Bone Resorption; Cell Differentiation; Humans; Inflammation; Osteogenesis; Tumor Necrosis Factor-alpha
PubMed: 33133025
DOI: 10.3389/fendo.2020.583561 -
Cellular & Molecular Biology Letters Sep 2022Osteoporotic fractures lead to increased disability and mortality in the elderly population. With the rapid increase in the aging population around the globe, more... (Review)
Review
Osteoporotic fractures lead to increased disability and mortality in the elderly population. With the rapid increase in the aging population around the globe, more effective treatments for osteoporosis and osteoporotic fractures are urgently required. The underlying molecular mechanisms of osteoporosis are believed to be due to the increased activity of osteoclasts, decreased activity of osteoblasts, or both, which leads to an imbalance in the bone remodeling process with accelerated bone resorption and attenuated bone formation. Currently, the available clinical treatments for osteoporosis have mostly focused on factors influencing bone remodeling; however, they have their own limitations and side effects. Recently, cytokine immunotherapy, gene therapy, and stem cell therapy have become new approaches for the treatment of various diseases. This article reviews the latest research on bone remodeling mechanisms, as well as how this underpins current and potential novel treatments for osteoporosis.
Topics: Aged; Bone Remodeling; Bone Resorption; Humans; Osteoclasts; Osteoporosis; Osteoporotic Fractures
PubMed: 36058940
DOI: 10.1186/s11658-022-00371-3 -
The Journal of Clinical Endocrinology... Mar 1992
Review
Topics: Amino Acids; Biomarkers; Bone Resorption; Bone and Bones; Humans
PubMed: 1740477
DOI: 10.1210/jcem.74.3.1740477 -
BioMed Research International 2022Periodontitis, a highly prevalent multicausal chronic inflammatory and destructive disease, develops as a result of complex host-parasite interactions. Dysbiotic... (Review)
Review
Periodontitis, a highly prevalent multicausal chronic inflammatory and destructive disease, develops as a result of complex host-parasite interactions. Dysbiotic bacterial biofilm in contact with the gingival tissues initiates a cascade of inflammatory events, mediated and modulated by the host's immune response, which is characterized by increased expression of several inflammatory mediators such as cytokines and chemokines in the connective tissue. If periodontal disease (PD) is left untreated, it results in the destruction of the supporting tissues around the teeth, including periodontal ligament, cementum, and alveolar bone, which lead to a wide range of disabilities and poor quality of life, thus imposing significant burdens. This process depends on the differentiation and activity of osteoclasts, the cells responsible for reabsorbing the bone tissue. Therefore, the inhibition of differentiation or activity of these cells is a promising strategy for controlling bone resorption. Several pharmacological drugs that target osteoclasts and inflammatory cells with immunomodulatory and anti-inflammatory effects, such as bisphosphonates, anti-RANK-L antibody, strontium ranelate, cathepsin inhibitors, curcumin, flavonoids, specialized proresolving mediators, and probiotics, were already described to manage inflammatory bone resorption during experimental PD progression in preclinical studies. Meantime, a growing number of studies have described the beneficial effects of herbal products in inhibiting bone resorption in experimental PD. Therefore, this review summarizes the role of several pharmacological drugs used for PD prevention and treatment and highlights the targeted action of all those drugs with antiresorptive properties. In addition, our review provides a timely and critical appraisal for the scientific rationale use of the antiresorptive and immunomodulatory medications in preclinical studies, which will help to understand the basis for its clinical application.
Topics: Alveolar Bone Loss; Bone Resorption; Humans; Osteoclasts; Periodontal Diseases; Periodontitis; Quality of Life
PubMed: 35547360
DOI: 10.1155/2022/5832009 -
International Journal of Molecular... Sep 2019Bone is a peculiar tissue subjected to a continuous process of self-renewal essential to assure the integrity of the skeleton and to explicate the endocrine functions.... (Review)
Review
Bone is a peculiar tissue subjected to a continuous process of self-renewal essential to assure the integrity of the skeleton and to explicate the endocrine functions. The study of bone diseases characterized by increased or reduced bone mass due to osteoclast alterations has been essential to understand the great role played by osteocalcin in the endocrine functions of the skeleton. The ability of osteoclasts to regulate the decarboxylation of osteocalcin and to control glucose metabolism, male fertility, and cognitive functions was demonstrated by the use of animal models. In this review we described how diseases characterized by defective and increased bone resorption activity, as osteopetrosis and osteoporosis, were essential to understand the involvement of bone tissue in whole body physiology. To translate this knowledge into humans, recently published reports on patients were described, but further studies should be performed to confirm this complex hormonal regulation in humans.
Topics: Animals; Bone Density; Bone Resorption; Endocrine System; Fertility; Glucose; Humans; Osteocalcin
PubMed: 31514440
DOI: 10.3390/ijms20184502 -
Osteoporosis International : a Journal... Sep 2013The transcription factor NF-κB is a family of proteins involved in signaling pathways essential for normal cellular functions and development. Deletion of various... (Review)
Review
The transcription factor NF-κB is a family of proteins involved in signaling pathways essential for normal cellular functions and development. Deletion of various components of this pathway resulted with abnormal skeletal development. Research in the last decade has established that NF-κB signaling mediates RANK ligand-induced osteoclastogenesis. Consistently, it was shown that inhibition of NF-κB was an effective approach to inhibit osteoclast formation and bone resorptive activity. Identification of the molecular machinery underlying NF-κB activation permitted osteoclast-specific deletion of the major components of this pathway. As a result, it was clear that deletion of members of the proximal IKK kinase complex and the distal NF-κB subunits and downstream regulators affected skeletal development. These studies provided several targets of therapeutic intervention in osteolytic diseases. NF-κB activity has been also described as the centerpiece of inflammatory responses and is considered a potent mediator of inflammatory osteolysis. Indeed, inflammatory insults exacerbate physiologic RANKL-induced NF-κB signals leading to exaggerated responses and to inflammatory osteolysis. These superimposed NF-κB activities appear to underlie several bone pathologies. This review will describe the individual roles of NF-κB molecules in bone resorption and inflammatory osteolysis.
Topics: Bone Resorption; Humans; NF-kappa B; Osteitis Deformans; Osteoclasts; Osteolysis; Periodontitis; Signal Transduction
PubMed: 23468073
DOI: 10.1007/s00198-013-2313-x