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Journal of Dental Research Dec 2010Bones provide mechanical and protective function, while also serving as housing for marrow and a site for regulation of calcium ion homeostasis. The properties of bones... (Review)
Review
Bones provide mechanical and protective function, while also serving as housing for marrow and a site for regulation of calcium ion homeostasis. The properties of bones do not remain constant with age; rather, they change throughout life, in some cases improving in function, but in others, function deteriorates. Here we review the modifications in the mechanical function and shape of bones, the bone cells, the matrix they produce, and the mineral that is deposited on this matrix, while presenting recent theories about the factors leading to these changes.
Topics: Aging; Animals; Biomechanical Phenomena; Bone Density; Bone Development; Bone Matrix; Bone and Bones; Humans; Models, Animal; Molecular Biology; Osteoporosis
PubMed: 20924069
DOI: 10.1177/0022034510377791 -
Orthopaedic Surgery Oct 2019Reconstruction of massive bone defects is challenging for orthopaedic clinicians, especially in cases of severe trauma and resection of tumors in various locales.... (Review)
Review
Reconstruction of massive bone defects is challenging for orthopaedic clinicians, especially in cases of severe trauma and resection of tumors in various locales. Autologous iliac crest bone graft (ICBG) is the "gold standard" for bone grafting. However, the limited availability and complications at donor sites resulted in seeking other options like allografts and bone graft substitutes. Demineralized bone matrix (DBM) is a form of allograft using acidic solution to remove mineral components, while leaving much of the proteinaceous components native to bone, with small amounts of calcium-based solids, inorganic phosphates, and some trace cell debris. It is an osteoconductive and osteoinductive biomaterial and is approved as a medical device for use in bone defects and spinal fusion. To pack consistently into the defect sites and stay firmly in the filling parts, DBM products have various forms combined with biocompatible viscous carriers, including sponges, strips, injectable putty, paste, and paste infused with chips. The present review aims to summarize the properties of various kind of viscous carriers and their clinical use combined with DBM in commercially available products. Given DBM'mercially available products. Given DBM;s long clinical track record and commercial accessibility in standard forms, opportunities to further develop and validate DBM as a versatile bone biomaterial in orthopaedic repair and regenerative medicine contexts are attractive.
Topics: Allografts; Biocompatible Materials; Bone Demineralization Technique; Bone Matrix; Bone Regeneration; Bone Substitutes; Bone Transplantation; Humans
PubMed: 31496049
DOI: 10.1111/os.12509 -
International Journal of Molecular... Sep 2022Bone mineralization entails two mineralization phases: primary and secondary mineralization. Primary mineralization is achieved when matrix vesicles are secreted by... (Review)
Review
Bone mineralization entails two mineralization phases: primary and secondary mineralization. Primary mineralization is achieved when matrix vesicles are secreted by osteoblasts, and thereafter, bone mineral density gradually increases during secondary mineralization. Nearby extracellular phosphate ions (PO) flow into the vesicles via membrane transporters and enzymes located on the vesicles' membranes, while calcium ions (Ca), abundant in the tissue fluid, are also transported into the vesicles. The accumulation of Ca and PO in the matrix vesicles induces crystal nucleation and growth. The calcium phosphate crystals grow radially within the vesicle, penetrate the vesicle's membrane, and continue to grow outside the vesicle, ultimately forming mineralized nodules. The mineralized nodules then attach to collagen fibrils, mineralizing them from the contact sites (i.e., collagen mineralization). Afterward, the bone mineral density gradually increases during the secondary mineralization process. The mechanisms of this phenomenon remain unclear, but osteocytes may play a key role; it is assumed that osteocytes enable the transport of Ca and PO through the canaliculi of the osteocyte network, as well as regulate the mineralization of the surrounding bone matrix via the Phex/SIBLINGs axis. Thus, bone mineralization is biologically regulated by osteoblasts and osteocytes.
Topics: Bone Matrix; Calcification, Physiologic; Collagen; Extracellular Matrix; Osteoblasts; Osteocytes
PubMed: 36077336
DOI: 10.3390/ijms23179941 -
Bone Research Nov 2023Matrix vesicles (MVs) have shown strong effects in diseases such as vascular ectopic calcification and pathological calcified osteoarthritis and in wound repair of the...
Matrix vesicles (MVs) have shown strong effects in diseases such as vascular ectopic calcification and pathological calcified osteoarthritis and in wound repair of the skeletal system due to their membranous vesicle characteristics and abundant calcium and phosphorus content. However, the role of MVs in the progression of osteoporosis is poorly understood. Here, we report that annexin A5, an important component of the matrix vesicle membrane, plays a vital role in bone matrix homeostasis in the deterioration of osteoporosis. We first identified annexin A5 from adherent MVs but not dissociative MVs of osteoblasts and found that it could be sharply decreased in the bone matrix during the occurrence of osteoporosis based on ovariectomized mice. We then confirmed its potential in mediating the mineralization of the precursor osteoblast lineage via its initial binding with collagen type I to achieve MV adhesion and the subsequent activation of cellular autophagy. Finally, we proved its protective role in resisting bone loss by applying it to osteoporotic mice. Taken together, these data revealed the importance of annexin A5, originating from adherent MVs of osteoblasts, in bone matrix remodeling of osteoporosis and provided a new strategy for the treatment and intervention of bone loss.
Topics: Animals; Mice; Annexin A5; Calcification, Physiologic; Bone Matrix; Vascular Calcification; Bone Diseases, Metabolic; Osteoporosis
PubMed: 37940665
DOI: 10.1038/s41413-023-00290-9 -
Current Osteoporosis Reports Aug 2019In perilacunar/canalicular remodeling (PLR), osteocytes dynamically resorb, and then replace, the organic and mineral components of the pericellular extracellular... (Review)
Review
PURPOSE OF REVIEW
In perilacunar/canalicular remodeling (PLR), osteocytes dynamically resorb, and then replace, the organic and mineral components of the pericellular extracellular matrix. Given the enormous surface area of the osteocyte lacuna-canalicular network (LCN), PLR is important for maintaining homeostasis of the skeleton. The goal of this review is to examine the motivations and critical considerations for the analysis of PLR, in both in vitro and in vivo systems.
RECENT FINDINGS
Morphological approaches alone are insufficient to elucidate the complex mechanisms regulating PLR in the healthy skeleton and in disease. Understanding the role and regulation of PLR will require the incorporation of standardized PLR outcomes as a routine part of skeletal phenotyping, as well as the development of improved molecular and cellular outcomes. Current PLR outcomes assess PLR enzyme expression, the LCN, and bone matrix composition and organization, among others. Here, we discuss current PLR outcomes and how they have been applied to study PLR induction and suppression in vitro and in vivo. Given the role of PLR in skeletal health and disease, integrated analysis of PLR has potential to elucidate new mechanisms by which osteocytes participate in skeletal health and disease.
Topics: Bone Matrix; Bone Remodeling; Carbonic Anhydrases; Cathepsin K; Cell Line; Homeostasis; Humans; Hydrogen-Ion Concentration; Imaging, Three-Dimensional; Matrix Metalloproteinases; Microscopy, Confocal; Microscopy, Electron, Scanning; Osteocytes; Proton-Translocating ATPases; X-Ray Microtomography
PubMed: 31227998
DOI: 10.1007/s11914-019-00514-0 -
Current Osteoporosis Reports Feb 2018Exosomes are membrane vesicles that are released by most cell types into the extracellular environment. The purpose of this article is to discuss the main morphological... (Review)
Review
PURPOSE OF REVIEW
Exosomes are membrane vesicles that are released by most cell types into the extracellular environment. The purpose of this article is to discuss the main morphological features and contents of bone-derived exosomes, as well as their major isolation and physical characterization techniques. Furthermore, we present various scenarios and discuss potential clinical applications of bone-derived exosomes in bone repair and regeneration.
RECENT FINDINGS
Exosomes were believed to be nanosized vesicles derived from the multivesicular body. Reports now suggest that nanovesicles could bud directly from the plasma membrane. However, the exosome cargo is cell-type specific and is derived from the parent cell. In the bone matrix, several intracellular proteins lacking a signal peptide are transported to the ECM by exosomes. Besides proteins, several mRNA, miRNA, and lipids are exported to the ECM by bone cells and bone marrow stromal cells. Recent evidence suggests that several of the functional components in the cargo could regulate processes of bone formation, inhibit osteoclast activity, and promote fracture repair. Exosomes are powerful cellular molecular machines produced without human intervention and packaged with physiological cargo that could be utilized for molecular therapy in several skeletal disorders such as osteoporosis, osteogenesis imperfecta, and fracture healing. Although much work has been done, there is a lot of information that is still unknown, as exosomes contain a multitude of molecules whose identity and function have yet to be identified.
Topics: Animals; Bone Matrix; Bone Regeneration; Exosomes; Humans; Osteogenesis
PubMed: 29372401
DOI: 10.1007/s11914-018-0419-y -
Frontiers in Endocrinology 2020Osteocytes make up 90-95% of the cellular content of bone and form a rich dendritic network with a vastly greater surface area than either osteoblasts or osteoclasts.... (Review)
Review
Osteocytes make up 90-95% of the cellular content of bone and form a rich dendritic network with a vastly greater surface area than either osteoblasts or osteoclasts. Osteocytes are well positioned to play a role in bone homeostasis by interacting directly with the matrix; however, the ability for these cells to modify bone matrix remains incompletely understood. With techniques for examining the nano- and microstructure of bone matrix components including hydroxyapatite and type I collagen becoming more widespread, there is great potential to uncover novel roles for the osteocyte in maintaining bone quality. In this review, we begin with an overview of osteocyte biology and the lacunar-canalicular system. Next, we describe recent findings from models of osteocytes, focusing on the transitions in cellular phenotype as they mature. Finally, we describe historical and current research on matrix alteration by osteocytes , focusing on the exciting potential for osteocytes to directly form, degrade, and modify the mineral and collagen in their surrounding matrix.
Topics: Animals; Bone Matrix; Bone Remodeling; Homeostasis; Humans; Minerals; Osteocytes; Osteogenesis
PubMed: 33537002
DOI: 10.3389/fendo.2020.578477 -
Advanced Drug Delivery Reviews Sep 2012Demineralized bone matrix (DBM) is an osteoconductive and osteoinductive commercial biomaterial and approved medical device used in bone defects with a long track record... (Review)
Review
Demineralized bone matrix (DBM) is an osteoconductive and osteoinductive commercial biomaterial and approved medical device used in bone defects with a long track record of clinical use in diverse forms. True to its name and as an acid-extracted organic matrix from human bone sources, DBM retains much of the proteinaceous components native to bone, with small amounts of calcium-based solids, inorganic phosphates and some trace cell debris. Many of DBM's proteinaceous components (e.g., growth factors) are known to be potent osteogenic agents. Commercially sourced as putty, paste, sheets and flexible pieces, DBM provides a degradable matrix facilitating endogenous release of these compounds to the bone wound sites where it is surgically placed to fill bone defects, inducing new bone formation and accelerating healing. Given DBM's long clinical track record and commercial accessibility in standard forms and sources, opportunities to further develop and validate DBM as a versatile bone biomaterial in orthopedic repair and regenerative medicine contexts are attractive.
Topics: Animals; Bone Demineralization Technique; Bone Matrix; Bone Regeneration; Bone Substitutes; Bone Transplantation; Bone and Bones; Humans; Osteogenesis
PubMed: 22728914
DOI: 10.1016/j.addr.2012.06.008 -
Current Osteoporosis Reports Jun 2018While thinning of the cortices or trabeculae weakens bone, age-related changes in matrix composition also lower fracture resistance. This review summarizes how the... (Review)
Review
PURPOSE OF REVIEW
While thinning of the cortices or trabeculae weakens bone, age-related changes in matrix composition also lower fracture resistance. This review summarizes how the organic matrix, mineral phase, and water compartments influence the mechanical behavior of bone, thereby identifying characteristics important to fracture risk.
RECENT FINDINGS
In the synthesis of the organic matrix, tropocollagen experiences various post-translational modifications that facilitate a highly organized fibril of collagen I with a preferred orientation giving bone extensibility and several toughening mechanisms. Being a ceramic, mineral is brittle but increases the strength of bone as its content within the organic matrix increases. With time, hydroxyapatite-like crystals experience carbonate substitutions, the consequence of which remains to be understood. Water participates in hydrogen bonding with organic matrix and in electrostatic attractions with mineral phase, thereby providing stability to collagen-mineral interface and ductility to bone. Clinical tools sensitive to age- and disease-related changes in matrix composition that the affect mechanical behavior of bone could potentially improve fracture risk assessment.
Topics: Biomechanical Phenomena; Bone Density; Bone Matrix; Bone and Bones; Cancellous Bone; Collagen Type I; Fractures, Bone; Glycation End Products, Advanced; Humans; Minerals; Protein Processing, Post-Translational; Tropocollagen; Water
PubMed: 29611037
DOI: 10.1007/s11914-018-0433-0 -
Frontiers in Bioscience (Landmark... Jan 2012Mammalian bones are composed of calcium phosphate crystals in a protein matrix. The major form of the calcium phosphate is hydroxyapatite. The most abundant matrix... (Review)
Review
Mammalian bones are composed of calcium phosphate crystals in a protein matrix. The major form of the calcium phosphate is hydroxyapatite. The most abundant matrix protein in bone is type I collagen. Collagen contributes to the mechanical properties of bone and is necessary for calcification of the tissue. In addition to collagen, several acidic proteins are present as minor components. Osteocalcin is a gamma-carboxyglutamic acid-containing protein of bone, which has an affinity to hydroxyapatite and can prevent crystal growth. Bone sialoprotein (BSP) and osteopontin are acidic glycophosphoproteins of bone. These proteins have RGD cell-attachment sequences and consecutive sequences of acidic amino acids. The poly glutamic acid sequences of BSP act as possible nucleation sites for hydroxyapatite crystals. Dentin phosphoprotein is the major non-collagenous protein of dentin. This protein has (Asp-Ser-Ser) repeat sequences, in which most of the Ser residues are phosphorylated. Some of these acidic matrix proteins are immobilized on the collagen fibrils and induce nucleation of hydroxyapatite crystals. They can also modulate crystal shape by adsorption on a specific face of the crystals.
Topics: Animals; Bone Matrix; Calcification, Physiologic; Proteins
PubMed: 22201843
DOI: 10.2741/4026