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Pharmacological Research Sep 2019Osteoporosis and osteopenia impact more than 54 million Americans, resulting in significant morbidity and mortality. Alterations in bone remodeling are the hallmarks for... (Review)
Review
Osteoporosis and osteopenia impact more than 54 million Americans, resulting in significant morbidity and mortality. Alterations in bone remodeling are the hallmarks for osteoporosis, and thus the development of novel treatments that will prevent or treat bone diseases would be clinically significant, and improve the quality of life for these patients. Bone remodeling involves the removal of old bone by osteoclasts and the formation of new bone by osteoblasts. This process is tightly coupled, and is essential for the maintenance of bone strength and integrity. Since the osteoclast is the only cell capable of bone resorption, the development of drugs to treat bone disorders has primarily focused on reducing osteoclast differentiation, maturation, and bone resorption mechanisms, and there are few treatments that actually increase bone formation. Evidence from observational, experimental, and clinical studies demonstrate a positive link between naturally occurring compounds and improved indices of bone health. While many natural extracts and compounds are reported to have beneficial effects on bone, only resveratrol, sulforaphane, specific phenolic acids and anthocyanins, have been shown to both increase bone formation and reduce resorption through their effects on the bone epigenome. Each of these compounds alters specific aspects of the bone epigenome to improve osteoblast differentiation, reduce osteoblast apoptosis, improve bone mineralization, and reduce osteoclast differentiation and function. This review focuses on these specific natural compounds and their epigenetic regulation of bone remodeling.
Topics: Animals; Biological Products; Bone Remodeling; Epigenesis, Genetic; Humans
PubMed: 31315065
DOI: 10.1016/j.phrs.2019.104350 -
Cold Spring Harbor Perspectives in... Aug 2018Parathyroid hormone (PTH) exerts profound effects on skeletal homeostasis through multiple cellular and molecular mechanisms. Continuous hyperparathyroidism causes net... (Review)
Review
Parathyroid hormone (PTH) exerts profound effects on skeletal homeostasis through multiple cellular and molecular mechanisms. Continuous hyperparathyroidism causes net loss of bone mass, despite accelerating bone formation by osteoblasts. Intermittent treatment with PTH analogs represents the only Food and Drug Administration (FDA)-approved bone anabolic osteoporosis treatment strategy. Functional PTH receptors are present on cells of the osteoblast lineage, ranging from early skeletal stem cells to matrix-embedded osteocytes. In addition, bone remodeling by osteoclasts liberates latent growth factors present within bone matrix. Here, we will provide an overview of the multiple cellular and molecular mechanisms through which PTH influences bone homeostasis. Notably, net skeletal effects of continuous versus intermittent can differ significantly. Where possible, we will highlight mechanisms through which continuous hyperparathyroidism leads to bone loss, and through which intermittent hyperparathyroidism boosts bone mass. Given the therapeutic usage of intermittent PTH (iPTH) treatment for osteoporosis, particular attention will be paid toward mechanisms underlying the bone anabolic effects of once daily PTH administration.
Topics: Animals; Bone Remodeling; CD8-Positive T-Lymphocytes; Humans; Mice; Models, Biological; Osteoclasts; Osteocytes; Osteoporosis; Parathyroid Hormone
PubMed: 29358318
DOI: 10.1101/cshperspect.a031237 -
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 -
European Journal of Cancer Care Nov 2017During life, bone undergoes modelling and remodelling in order to grow or change shape. Bone modelling is the process by which bones change shape or size in response to... (Review)
Review
During life, bone undergoes modelling and remodelling in order to grow or change shape. Bone modelling is the process by which bones change shape or size in response to physiologic influences or mechanical forces that are encountered by the skeleton, while bone remodelling takes place so that bone may maintain its strength and mineral homeostasis. During early childhood, both bone modelling (the formation and shaping of bone) and bone remodelling (the replacement or renewal of old bone) occur. The predominant process in childhood is bone modelling, while in adulthood bone remodelling predominates. The exception to this is after a fracture when we see massive increases in bone formation. During childhood and adolescence growth occurs in the bones longitudinally and radially, while in the growth plates it occurs longitudinally, thus promoting growth in size. Cartilage first proliferates in the epiphyseal and metaphyseal areas of long bones before undergoing mineralisation to form new bone.
Topics: Bone Development; Bone Remodeling; Bone Resorption; Calcification, Physiologic; Cartilage; Humans; Osteoblasts; Osteoclasts; Osteocytes; Osteogenesis; Stress, Mechanical
PubMed: 28786518
DOI: 10.1111/ecc.12740 -
Frontiers in Public Health 2022Ferroptosis was induced the programmed cell death with iron overload Fenton reaction. Currently, ferroptosis has not been studied thoroughly. Existing studies have... (Review)
Review
Ferroptosis was induced the programmed cell death with iron overload Fenton reaction. Currently, ferroptosis has not been studied thoroughly. Existing studies have confirmed that ferroptosis involves the metabolisms of the Fe, lipids, amino acid, each mechanism is mutually independent but interrelated, and they are formed a complex regulatory network. Other evidence supports that ferroptosis is participated osteoporotic bone remodeling, predominantly affecting the interaction between bone formation and bone resorption, explicitly bone resorption exceeded bone formation. Based on previous studies, this review will summarize the regulatory network mechanism of ferroptosis on bone remodeling and reveal the role of ferroptosis in osteoporosis (OP).
Topics: Bone Remodeling; Bone Resorption; Ferroptosis; Humans; Osteoporosis
PubMed: 35844870
DOI: 10.3389/fpubh.2022.910675 -
Stem Cell Reviews and Reports Aug 2023As a highly dynamic organ, bone changes during throughout a person's life. This process is referred to as 'bone remodeling' and it involves two stages - a well-balanced... (Review)
Review
As a highly dynamic organ, bone changes during throughout a person's life. This process is referred to as 'bone remodeling' and it involves two stages - a well-balanced osteoclastic bone resorption and an osteoblastic bone formation. Under normal physiological conditions bone remodeling is highly regulated that ensures tight coupling between bone formation and resorption, and its disruption results in a bone metabolic disorder, most commonly osteoporosis. Though osteoporosis is one of the most prevalent skeletal ailments that affect women and men aged over 40 of all races and ethnicities, currently there are few, if any safe and effective therapeutic interventions available. Developing state-of-the-art cellular systems for bone remodeling and osteoporosis can provide important insights into the cellular and molecular mechanisms involved in skeletal homeostasis and advise better therapies for patients. This review describes osteoblastogenesis and osteoclastogenesis as two vital processes for producing mature, active bone cells in the context of interactions between cells and the bone matrix. In addition, it considers current approaches in bone tissue engineering, pointing out cell sources, core factors and matrices used in scientific practice for modeling bone diseases and testing drugs. Finally, it focuses on the challenges that bone regenerative medicine is currently facing.
Topics: Humans; Female; Adult; Middle Aged; Bone Remodeling; Bone Resorption; Bone and Bones; Bone Diseases; Osteoporosis
PubMed: 37204634
DOI: 10.1007/s12015-023-10558-6 -
Progress in Orthodontics Jun 2018In this review, most of the known and postulated mechanisms of osteopontin (OPN) and its role in bone remodeling and orthodontic tooth movement are discussed based on... (Review)
Review
In this review, most of the known and postulated mechanisms of osteopontin (OPN) and its role in bone remodeling and orthodontic tooth movement are discussed based on available literature. OPN, a multifunctional protein, is considered crucial for bone remodeling, biomineralization, and periodontal remodeling during mechanical tension and stress (orthodontic tooth movement). It contributes to bone remodeling by promoting osteoclastogenesis and osteoclast activity through CD44- and αvβ3-mediated cell signaling. Further, it has a definitive role in bone remodeling by the formation of podosomes, osteoclast survival, and osteoclast motility. OPN has been shown to have a regulatory effect on hydroxyapatite crystal (HAP) growth and potently inhibits the mineralization of osteoblast cultures in a phosphate-dependent manner. Bone remodeling is vital for orthodontic tooth movement. Significant compressive and tensional forces on the periodontium induce the signaling pathways mediated by various osteogenic genes including OPN, bone sialoprotein, Osterix, and osteocalcin. The signaling pathways involved in the regulation of OPN and its effect on the periodontal tissues during orthodontic tooth movement are further discussed in this review. A limited number of studies have suggested the use of OPN as a biomarker to assess orthodontic treatment. Furthermore, the association of single nucleotide polymorphisms (SNPs) in OPN coding gene Spp1 with orthodontically induced root resorption remains largely unexplored. Accordingly, future research directions for OPN are outlined in this review.
Topics: Animals; Bone Remodeling; Humans; Osteopontin; Tooth Movement Techniques
PubMed: 29938297
DOI: 10.1186/s40510-018-0216-2 -
Frontiers of Oral Biology 2016Bone remodeling is a highly coordinated process responsible for bone resorption and formation. It is initiated and modulated by a number of factors including... (Review)
Review
Bone remodeling is a highly coordinated process responsible for bone resorption and formation. It is initiated and modulated by a number of factors including inflammation, changes in hormonal levels and lack of mechanical stimulation. Bone remodeling involves the removal of mineralized bone by osteoclasts followed by the formation of bone matrix through osteoblasts that subsequently becomes mineralized. In addition to the traditional bone cells (osteoclasts, osteoblasts and osteocytes) that are necessary for bone remodeling, several immune cells such as polymorphonuclear neutrophils, B cells and T cells have also been implicated in bone remodelling. Through the receptor activator of nuclear factor-x03BA;B/receptor activator of the NF-x03BA;B ligand/osteoprotegerin system the process of bone resorption is initiated and subsequent formation is tightly coupled. Mediators such as prostaglandins, interleukins, chemokines, leukotrienes, growth factors, wnt signalling and bone morphogenetic proteins are involved in the regulation of bone remodeling. We discuss here cells and mediators involved in the cellular and molecular machanisms of bone resorption and bone formation.
Topics: Bone Remodeling; Bone Resorption; Calcification, Physiologic; Humans; Inflammation Mediators; Lymphocytes; Neutrophils; Osteoblasts; Osteoclasts; Osteogenesis
PubMed: 26599113
DOI: 10.1159/000351895 -
Journal of the World Federation of... Oct 2022With increased understanding of orthodontic tooth movement (OTM) in recent years, neural regulation of OTM has become an emerging and expanding area of research.... (Review)
Review
With increased understanding of orthodontic tooth movement (OTM) in recent years, neural regulation of OTM has become an emerging and expanding area of research. Numerous studies have shown that the nervous system, including the central and peripheral systems, regulates bone remodeling through various neuropeptides, receptor expression, etc. OTM is a unique periodontal tissue remodeling process induced by mechanical force, including changes in the periodontal ligament metabolism and alveolar bone remodeling. Various studies have shown that the nervous system participates in the OTM process and regulates the periodontal ligament metabolism. This review summarizes the current researches on neural regulation of bone remodeling and the biological responses within the periodontal ligamentduring OTM under therapeutic loading. We also discuss the issues that remain to be addressed in this field. The exploration of neural regulation on OTM not only assists us to understand the mechanism of OTM more thoroughly, but also provides a new insight to accelerate tooth movement in the future.
Topics: Bone Remodeling; Mechanical Phenomena; Neuropeptides; Periodontal Ligament; Tooth Movement Techniques
PubMed: 36175332
DOI: 10.1016/j.ejwf.2022.08.003 -
Frontiers in Endocrinology 2021Flavonoids are polyphenolic compounds spotted in various fruits, vegetables, barks, tea plants, and stems and many more natural commodities. They have a multitude of... (Review)
Review
Flavonoids are polyphenolic compounds spotted in various fruits, vegetables, barks, tea plants, and stems and many more natural commodities. They have a multitude of applications through their anti-inflammatory, anti-oxidative, anti-carcinogenic properties, along with the ability to assist in the stimulation of bone formation. Bone, a rigid connective body tissue made up of cells embedded in a mineralised matrix is maintained by an assemblage of pathways assisting osteoblastogenesis and osteoclastogenesis. These have a significant impact on a plethora of bone diseases. The homeostasis between osteoblast and osteoclast formation decides the integrity and structure of the bone. The flavonoids discussed here are quercetin, kaempferol, icariin, myricetin, naringin, daidzein, luteolin, genistein, hesperidin, apigenin and several other flavonoids. The effects these flavonoids have on the mitogen activated protein kinase (MAPK), nuclear factor kappa β (NF-kβ), Wnt/β-catenin and bone morphogenetic protein 2/SMAD (BMP2/SMAD) signalling pathways, and apoptotic pathways lead to impacts on bone remodelling. In addition, these polyphenols regulate angiogenesis, decrease the levels of inflammatory cytokines and play a crucial role in scavenging reactive oxygen species (ROS). Considering these important effects of flavonoids, they may be regarded as a promising agent in treating bone-related ailments in the future.
Topics: Animals; Anti-Inflammatory Agents; Bone Diseases; Bone Remodeling; Flavonoids; Humans; Osteoblasts; Osteoclasts; Osteogenesis; Signal Transduction
PubMed: 34887836
DOI: 10.3389/fendo.2021.779638