-
Annals of Clinical Biochemistry May 2018The bone remodelling cycle replaces old and damaged bone and is a highly regulated, lifelong process essential for preserving bone integrity and maintaining mineral... (Review)
Review
The bone remodelling cycle replaces old and damaged bone and is a highly regulated, lifelong process essential for preserving bone integrity and maintaining mineral homeostasis. During the bone remodelling cycle, osteoclastic resorption is tightly coupled to osteoblastic bone formation. The remodelling cycle occurs within the basic multicellular unit and comprises five co-ordinated steps; activation, resorption, reversal, formation and termination. These steps occur simultaneously but asynchronously at multiple different locations within the skeleton. Study of rare human bone disease and animal models have helped to elucidate the cellular and molecular mechanisms that regulate the bone remodelling cycle. The key signalling pathways controlling osteoclastic bone resorption and osteoblastic bone formation are receptor activator of nuclear factor-κB (RANK)/RANK ligand/osteoprotegerin and canonical Wnt signalling. Cytokines, growth factors and prostaglandins act as paracrine regulators of the cycle, whereas endocrine regulators include parathyroid hormone, vitamin D, calcitonin, growth hormone, glucocorticoids, sex hormones, and thyroid hormone. Disruption of the bone remodelling cycle and any resulting imbalance between bone resorption and formation leads to metabolic bone disease, most commonly osteoporosis. The advances in understanding the cellular and molecular mechanisms underlying bone remodelling have also provided targets for pharmacological interventions which include antiresorptive and anabolic therapies. This review will describe the remodelling process and its regulation, discuss osteoporosis and summarize the commonest pharmacological interventions used in its management.
Topics: Animals; Bone Density Conservation Agents; Bone Remodeling; Bone Resorption; Homeostasis; Humans; Osteoporosis; Osteoprotegerin; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Wnt Signaling Pathway
PubMed: 29368538
DOI: 10.1177/0004563218759371 -
Physiological Reviews Jan 2022Osteocytes, former osteoblasts encapsulated by mineralized bone matrix, are far from being passive and metabolically inactive bone cells. Instead, osteocytes are... (Review)
Review
Osteocytes, former osteoblasts encapsulated by mineralized bone matrix, are far from being passive and metabolically inactive bone cells. Instead, osteocytes are multifunctional and dynamic cells capable of integrating hormonal and mechanical signals and transmitting them to effector cells in bone and in distant tissues. Osteocytes are a major source of molecules that regulate bone homeostasis by integrating both mechanical cues and hormonal signals that coordinate the differentiation and function of osteoclasts and osteoblasts. Osteocyte function is altered in both rare and common bone diseases, suggesting that osteocyte dysfunction is directly involved in the pathophysiology of several disorders affecting the skeleton. Advances in osteocyte biology initiated the development of novel therapeutics interfering with osteocyte-secreted molecules. Moreover, osteocytes are targets and key distributors of biological signals mediating the beneficial effects of several bone therapeutics used in the clinic. Here we review the most recent discoveries in osteocyte biology demonstrating that osteocytes regulate bone homeostasis and bone marrow fat via paracrine signaling, influence body composition and energy metabolism via endocrine signaling, and contribute to the damaging effects of diabetes mellitus and hematologic and metastatic cancers in the skeleton.
Topics: Animals; Bone Remodeling; Bone Resorption; Cell Differentiation; Humans; Osteoclasts; Osteocytes; Osteogenesis
PubMed: 34337974
DOI: 10.1152/physrev.00043.2020 -
Journal of Bone and Mineral Research :... Mar 2023Bone remodeling in the adult skeleton facilitates the removal and replacement of damaged and old bone to maintain bone quality. Tight coordination of bone resorption and... (Review)
Review
Bone remodeling in the adult skeleton facilitates the removal and replacement of damaged and old bone to maintain bone quality. Tight coordination of bone resorption and bone formation during remodeling crucially maintains skeletal mass. Increasing evidence suggests that many cell types beyond osteoclasts and osteoblasts support bone remodeling, including macrophages and other myeloid lineage cells. Herein, we discuss the origin and functions for macrophages in the bone microenvironment, tissue resident macrophages, osteomacs, as well as newly identified osteomorphs that result from osteoclast fission. We also touch on the role of macrophages during inflammatory bone resorption. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Topics: Humans; Cell Differentiation; Bone Remodeling; Osteoclasts; Macrophages; Bone Resorption; Osteoblasts; Osteogenesis
PubMed: 36651575
DOI: 10.1002/jbmr.4773 -
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 -
Physiology (Bethesda, Md.) May 2016Bone remodeling is essential for adult bone homeostasis. It comprises two phases: bone formation and resorption. The balance between the two phases is crucial for... (Review)
Review
Bone remodeling is essential for adult bone homeostasis. It comprises two phases: bone formation and resorption. The balance between the two phases is crucial for sustaining bone mass and systemic mineral homeostasis. This review highlights recent work on physiological bone remodeling and discusses our knowledge of how systemic and growth factors regulate this process.
Topics: Animals; Bone Remodeling; Bone Resorption; Bone and Bones; Calcium; Homeostasis; Humans; Intercellular Signaling Peptides and Proteins
PubMed: 27053737
DOI: 10.1152/physiol.00061.2014 -
Annual Review of Physiology Feb 2020Osteocytes are an ancient cell, appearing in fossilized skeletal remains of early fish and dinosaurs. Despite its relative high abundance, even in the context of... (Review)
Review
Osteocytes are an ancient cell, appearing in fossilized skeletal remains of early fish and dinosaurs. Despite its relative high abundance, even in the context of nonskeletal cells, the osteocyte is perhaps among the least studied cells in all of vertebrate biology. Osteocytes are cells embedded in bone, able to modify their surrounding extracellular matrix via specialized molecular remodeling mechanisms that are independent of the bone forming osteoblasts and bone-resorbing osteoclasts. Osteocytes communicate with osteoclasts and osteoblasts via distinct signaling molecules that include the RankL/OPG axis and the Sost/Dkk1/Wnt axis, among others. Osteocytes also extend their influence beyond the local bone environment by functioning as an endocrine cell that controls phosphate reabsorption in the kidney, insulin secretion in the pancreas, and skeletal muscle function. These cells are also finely tuned sensors of mechanical stimulation to coordinate with effector cells to adjust bone mass, size, and shape to conform to mechanical demands.
Topics: Animals; Bone Remodeling; Bone and Bones; Fibroblast Growth Factor-23; Humans; Osteocytes
PubMed: 32040934
DOI: 10.1146/annurev-physiol-021119-034332 -
Seminars in Immunopathology Sep 2019Osteoclasts are bone-resorbing cells that play an essential role in the remodeling of the bone. Defects in osteoclasts thus result in unbalanced bone remodeling, leading... (Review)
Review
Osteoclasts are bone-resorbing cells that play an essential role in the remodeling of the bone. Defects in osteoclasts thus result in unbalanced bone remodeling, leading to numerous pathological conditions such as osteoporosis, bone metastasis, and inflammatory bone erosion. Metabolism is any process a cell utilizes to meet its energetic demand for biological functions. Along with signaling pathways and osteoclast-specific gene expression programs, osteoclast differentiation activates metabolic programs. The energy generated from metabolic reprogramming in osteoclasts not only supports the phenotypic changes from mononuclear precursor cells to multinuclear osteoclasts, but also facilitates bone resorption, a major function of terminally differentiated, mature osteoclasts. While oxidative phosphorylation is studied as a major metabolic pathway that fulfills the energy demands of osteoclasts, all metabolic pathways are closely interconnected. Therefore, it remains important to understand the various aspects of osteoclast metabolism, including the roles and effects of glycolysis, glutaminolysis, fatty acid synthesis, and fatty acid oxidation. Targeting the pathways associated with metabolic reprogramming has shown beneficial effects on pathological conditions. As a result, it is clear that a deeper understanding of metabolic regulation in osteoclasts will offer broader translational potential for the treatment of human bone disorders.
Topics: Animals; Bone Remodeling; Bone Resorption; Bone and Bones; Cellular Reprogramming; Energy Metabolism; Glycolysis; Humans; Lipid Metabolism; Mitochondria; Organelle Biogenesis; Osteoclasts; Oxidative Phosphorylation; Signal Transduction; TOR Serine-Threonine Kinases
PubMed: 31552471
DOI: 10.1007/s00281-019-00757-0 -
Journal of Musculoskeletal & Neuronal... Sep 2020Understanding how bones are innately designed, robustly developed and delicately maintained through intricate anatomical features and physiological processes across the... (Review)
Review
Understanding how bones are innately designed, robustly developed and delicately maintained through intricate anatomical features and physiological processes across the lifespan is vital to inform our assessment of normal bone health, and essential to aid our interpretation of adverse clinical outcomes affecting bone through primary or secondary causes. Accordingly this review serves to introduce new researchers and clinicians engaging with bone and mineral metabolism, and provide a contemporary update for established researchers or clinicians. Specifically, we describe the mechanical and non-mechanical functions of the skeleton; its multidimensional and hierarchical anatomy (macroscopic, microscopic, organic, inorganic, woven and lamellar features); its cellular and hormonal physiology (deterministic and homeostatic processes that govern and regulate bone); and processes of mechanotransduction, modelling, remodelling and degradation that underpin bone adaptation or maladaptation. In addition, we also explore commonly used methods for measuring bone metabolic activity or material features (imaging or biochemical markers) together with their limitations.
Topics: Bone Remodeling; Bone and Bones; Humans
PubMed: 32877972
DOI: No ID Found -
European Cells & Materials Jun 2018Calcium and vitamin D are essential for maintaining bone health. Therefore, deficiencies in calcium and vitamin D are major risk factors for osteoporosis development.... (Review)
Review
Calcium and vitamin D are essential for maintaining bone health. Therefore, deficiencies in calcium and vitamin D are major risk factors for osteoporosis development. Because sufficient amounts of calcium are also required for fracture-callus mineralisation, compromised bone repair that is frequently observed in osteoporotic patients might be attributed to calcium and vitamin D deficiencies. Consequently, calcium and vitamin D supplementation represents a potential strategy for treating compromised fracture healing in osteoporotic patients. Growing clinical evidence suggests that a fracture event may induce post-traumatic bone loss in the non-fractured skeleton, particularly in osteoporotic patients, which might further exacerbate osteoporosis and increase the risk of secondary fractures. Because the skeleton represents the main source of calcium, which is increasingly required during fracture-callus mineralisation, post-traumatic calcium mobilisation might occur under conditions of insufficient calcium and vitamin D status. However, to date, investigations of the roles of calcium and vitamin D in bone repair and post-traumatic bone turnover are very limited. The current review summarises the state of the literature, focusing on the role of calcium and vitamin D in fracture healing and post-traumatic bone turnover, and critically discusses the therapeutic potential of calcium and vitamin D supplementation in this context.
Topics: Animals; Bone Remodeling; Calcium; Fracture Healing; Fractures, Bone; Humans; Vitamin D; Wounds and Injuries
PubMed: 29931664
DOI: 10.22203/eCM.v035a25 -
Frontiers in Endocrinology 2022Bone homeostasis involves bone formation and bone resorption, which are processes that maintain skeletal health. Oxidative stress is an independent risk factor, causing... (Review)
Review
Bone homeostasis involves bone formation and bone resorption, which are processes that maintain skeletal health. Oxidative stress is an independent risk factor, causing the dysfunction of bone homeostasis including osteoblast-induced osteogenesis and osteoclast-induced osteoclastogenesis, thereby leading to bone-related diseases, especially osteoporosis. Autophagy is the main cellular stress response system for the limination of damaged organelles and proteins, and it plays a critical role in the differentiation, apoptosis, and survival of bone cells, including bone marrow stem cells (BMSCs), osteoblasts, osteoclasts, and osteocytes. High evels of reactive oxygen species (ROS) induced by oxidative stress induce autophagy to protect against cell damage or even apoptosis. Additionally, pathways such as ROS/FOXO3, ROS/AMPK, ROS/Akt/mTOR, and ROS/JNK/c-Jun are involved in the regulation of oxidative stress-induced autophagy in bone cells, including osteoblasts, osteocytes and osteoclasts. This review discusses how autophagy regulates bone formation and bone resorption following oxidative stress and summarizes the potential protective mechanisms exerted by autophagy, thereby providing new insights regarding bone remodeling and potential therapeutic targets for osteoporosis.
Topics: Autophagy; Bone Remodeling; Bone Resorption; Humans; Osteoporosis; Oxidative Stress; Reactive Oxygen Species
PubMed: 35846332
DOI: 10.3389/fendo.2022.898634