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Nature Reviews. Molecular Cell Biology Nov 2020Bone development occurs through a series of synchronous events that result in the formation of the body scaffold. The repair potential of bone and its surrounding... (Review)
Review
Bone development occurs through a series of synchronous events that result in the formation of the body scaffold. The repair potential of bone and its surrounding microenvironment - including inflammatory, endothelial and Schwann cells - persists throughout adulthood, enabling restoration of tissue to its homeostatic functional state. The isolation of a single skeletal stem cell population through cell surface markers and the development of single-cell technologies are enabling precise elucidation of cellular activity and fate during bone repair by providing key insights into the mechanisms that maintain and regenerate bone during homeostasis and repair. Increased understanding of bone development, as well as normal and aberrant bone repair, has important therapeutic implications for the treatment of bone disease and ageing-related degeneration.
Topics: Animals; Bone Development; Bone Diseases; Bone and Bones; Humans; Regeneration
PubMed: 32901139
DOI: 10.1038/s41580-020-00279-w -
Bone Nov 2015The development of the vertebrate skeleton reflects its evolutionary history. Cartilage formation came before biomineralization and a head skeleton evolved before the... (Review)
Review
The development of the vertebrate skeleton reflects its evolutionary history. Cartilage formation came before biomineralization and a head skeleton evolved before the formation of axial and appendicular skeletal structures. This review describes the processes that result in endochondral and intramembranous ossification, the important roles of growth and transcription factors, and the consequences of mutations in some of the genes involved. Following a summary of the origin of cartilage, muscle, and tendon cell lineages in the axial skeleton, we discuss the role of muscle forces in the formation of skeletal architecture and assembly of musculoskeletal functional units. Finally, ontogenetic patterning of bones in response to mechanical loading is reviewed.This article is part of a Special Issue entitled "Muscle Bone Interactions".
Topics: Animals; Bone Development; Chondrogenesis; Humans; Osteogenesis; Tendons; Transcription Factors
PubMed: 26453494
DOI: 10.1016/j.bone.2015.04.035 -
Ciba Foundation Symposium 1988The sequential cellular and molecular details of the initial embryonic formation of bone can be used to gain insight into the control of this process and subsequent bone... (Review)
Review
The sequential cellular and molecular details of the initial embryonic formation of bone can be used to gain insight into the control of this process and subsequent bone physiology and repair. The functioning of osteogenic cells is governed by a complex balance between the intrinsic capacities of these cells in the context of extrinsic information and signalling. As with other mesenchymal tissues, the balance of intrinsic versus extrinsic capacities and influences is central to understanding both the sequence and consequence of bone development. It has been suggested that the cartilaginous model which forms at the centre of limbs is responsible for, and provides the scaffolding for, subsequent bone formation. Our recent studies of the embryonic chick tibia indicate that osteogenic progenitor cells are observed before the formation of the chondrogenic core. In particular, a layer of four to six cells, referred to as Stacked Cells, forms around a prechondrogenic core of undifferentiated cells. These osteoprogenitor cells give rise to all of the newly forming bone. Importantly, this newly forming bone arises outside and away from the chondrogenic core in a manner similar to the intramembranous bone formation seen in calvariae. Indeed, the cartilaginous core is replaced not by bone but by vascular and marrow tissues. The interplay between the osteogenic collar and the chondrogenic core provides an environment which stimulates the further differentiation of the cartilage core into hypertrophic cartilage and eventually renders this core replaceable by vascular and marrow tissue. There is an intimate relationship between the osteogenic cells and the vasculature which is obligatory for active bone formation. Bone formation in long bones, such as the tibia, as well as in the calvaria seems to proceed in a similar manner, with vascular tissue interaction being the most important aspect of successful osteogenesis, as opposed to the presence or interaction of cartilage. Our studies have focused on the development of long bones in aves, but detailed study of mouse and man indicates that many of the general features observed for birds apply to bone development in mammals. It is our current thesis that the general rules governing embryonic formation of long bones also apply to the formation of ectopic bone and are related to aspects of fracture repair.
Topics: Animals; Bone Development; Chick Embryo; Osteogenesis
PubMed: 3068015
DOI: 10.1002/9780470513637.ch2 -
Bone Feb 2021Epigenetic regulation is critical for proper bone development. Evidence from a large body of published literature informs us that microRNAs (miRNAs) are important... (Review)
Review
Epigenetic regulation is critical for proper bone development. Evidence from a large body of published literature informs us that microRNAs (miRNAs) are important epigenetic factors that control many aspects of bone development, homeostasis, and repair processes. These small non-coding RNAs function at the post-transcriptional level to suppress expression of specific target genes. Many target genes may be affected by one miRNA resulting in alteration in cellular pathways and networks. Therefore, changes in levels or activity of a specific miRNA (e.g. via genetic mutations, disease scenarios, or by over-expression or inhibition strategies in vitro or in vivo) can lead to substantial changes in cell processes including proliferation, metabolism, apoptosis and differentiation. In this review, Section 1 briefly covers general background information on processes that control bone development as well as the biogenesis and function of miRNAs. In Section 2, we discuss the importance of miRNAs in skeletal development based on findings from in vivo mouse models and human clinical reports. Section 3 focuses on describing more recent data from the last three years related to miRNA regulation of osteoblast differentiation in vitro. Some of these studies also involve utilization of an in vivo rodent model to study the effects of miRNA modulation in scenarios of osteoporosis, bone repair or ectopic bone formation. In Section 4, we provide some recent information from studies analyzing the potential of miRNA-mediated crosstalk in bone and how exosomes containing miRNAs from one bone cell may affect the differentiation or function of another bone cell type. We then conclude by summarizing where the field currently stands with respect to miRNA-mediated regulation of osteogenesis and how information gained from developmental processes can be instructive in identifying potential therapeutic miRNA targets for the treatment of certain bone conditions.
Topics: Animals; Bone Development; Cell Differentiation; Epigenesis, Genetic; Mice; MicroRNAs; Osteogenesis
PubMed: 33220505
DOI: 10.1016/j.bone.2020.115760 -
Birth Defects Research Sep 2018Evaluation of the skeleton in laboratory animals is a standard component of developmental toxicology testing. Standard methods of performing the evaluation have been... (Review)
Review
Evaluation of the skeleton in laboratory animals is a standard component of developmental toxicology testing. Standard methods of performing the evaluation have been established, and modification of the evaluation using imaging technologies is under development. The embryology of the rodent, rabbit, and primate skeleton has been characterized in detail and summarized herein. The rich literature on variations and malformations in skeletal development that can occur in the offspring of normal animals and animals exposed to test articles in toxicology studies is reviewed. These perturbations of skeletal development include ossification delays, alterations in number, shape, and size of ossification centers, and alterations in numbers of ribs and vertebrae. Because the skeleton is undergoing developmental changes at the time fetuses are evaluated in most study designs, transient delays in development can produce apparent findings of abnormal skeletal structure. The determination of whether a finding represents a permanent change in embryo development with adverse consequences for the organism is important in study interpretation. Knowledge of embryological processes and schedules can assist in interpretation of skeletal findings.
Topics: Animals; Bone Development; Bone and Bones; Disease Models, Animal; Drug-Related Side Effects and Adverse Reactions; Embryology; Embryonic Development; Fetus; Humans; Mammals; Organogenesis; Primates; Rabbits; Rodentia; Skeleton
PubMed: 29921029
DOI: 10.1002/bdr2.1350 -
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 -
Archives of Biochemistry and Biophysics Nov 2014Bone-forming cells originate from distinct embryological layers, mesoderm (axial and appendicular bones) and ectoderm (precursor of neural crest cells, which mainly form... (Review)
Review
Bone-forming cells originate from distinct embryological layers, mesoderm (axial and appendicular bones) and ectoderm (precursor of neural crest cells, which mainly form facial bones). These cells will develop bones by two principal mechanisms: intramembranous and endochondral ossification. In both cases, condensation of multipotent mesenchymal cells occurs, at the site of the future bone, which differentiate into bone and cartilage-forming cells. During long bone development, an initial cartilaginous template is formed and replaced by bone in a coordinated and refined program involving chondrocyte proliferation and maturation, vascular invasion, recruitment of adult stem cells and intense remodeling of cartilage and bone matrix. Matrix metalloproteinases (MMPs) are the most important enzymes for cleaving structural components of the extracellular matrix (ECM), as well as other non-ECM molecules in the ECM space, pericellular perimeter and intracellularly. Thus, the bioactive molecules generated act on several biological events, such as development, tissue remodeling and homeostasis. Since the discovery of collagenase in bone cells, more than half of the MMP members have been detected in bone tissues under both physiological and pathological conditions. Pivotal functions of MMPs during development and bone regeneration have been revealed by knockout mouse models, such as chondrocyte proliferation and differentiation, osteoclast recruitment and function, bone modeling, coupling of bone resorption and formation (bone remodeling), osteoblast recruitment and survival, angiogenesis, osteocyte viability and function (biomechanical properties); as such alterations in MMP function may alter bone quality. In this review, we look at the principal properties of MMPs and their inhibitors (TIMPs and RECK), provide an up-date on their known functions in bone development and remodeling and discuss their potential application to Bone Bioengineering.
Topics: Animals; Bone Development; Bone Remodeling; Bone and Bones; Humans; Matrix Metalloproteinases; Models, Biological; Osteogenesis; Tissue Engineering
PubMed: 25157440
DOI: 10.1016/j.abb.2014.07.034 -
Cell Stem Cell Dec 2021Multiple distinct types of skeletal progenitors have been shown to contribute to endochondral bone development and maintenance. However, the division of labor and...
Multiple distinct types of skeletal progenitors have been shown to contribute to endochondral bone development and maintenance. However, the division of labor and hierarchical relationship between different progenitor populations remain undetermined. Here we developed dual-recombinase fate-mapping systems to capture the skeletal progenitor transition during postnatal bone formation. We showed that postnatal osteoblasts arose primarily from chondrocytes before adolescence and from Lepr bone marrow stromal cells (BMSCs) after adolescence. This transition occurred in the diaphysis during adolescence and progressively spread to the metaphysis. The osteoblast-forming Lepr BMSCs derived primarily from fetal Col2 cells. Conditional deletion of Runx2 from perinatal chondrocytes and adult Lepr BMSCs impaired bone lengthening and thickening, respectively. Forced running increased osteoblast formation by perinatal chondrocytes but not by adult Lepr BMSCs. Thus, the short-term developmental skeletal progenitors generated the long-term adult skeletal progenitors. They sequentially control the growth and maintenance of endochondral bones.
Topics: Bone Development; Chondrocytes; Mesenchymal Stem Cells; Osteoblasts; Osteogenesis
PubMed: 34499868
DOI: 10.1016/j.stem.2021.08.010 -
International Journal of Molecular... Apr 2015MicroRNAs (miRNAs) are endogenous small noncoding ~22-nt RNAs, which have been reported to play a crucial role in maintaining bone development and metabolism.... (Review)
Review
MicroRNAs (miRNAs) are endogenous small noncoding ~22-nt RNAs, which have been reported to play a crucial role in maintaining bone development and metabolism. Osteogenesis originates from mesenchymal stem cells (MSCs) differentiating into mature osteoblasts and each period of bone formation is inseparable from the delicate regulation of various miRNAs. Of note, apprehending the sophisticated circuit between miRNAs and osteogenic homeostasis is of great value for artificial skeletal regeneration for severe bone defects. In this review, we highlight how different miRNAs interact with diverse osteo-related genes and endeavor to sketch the contours of potential manipulations of miRNA-modulated bone repair.
Topics: Animals; Bone Development; Bone and Bones; Cell Differentiation; Humans; MicroRNAs; Osteoblasts; Osteogenesis; Regeneration
PubMed: 25872144
DOI: 10.3390/ijms16048227 -
International Journal of Molecular... Jul 2021Interaction between endothelial cells and osteoblasts is essential for bone development and homeostasis. This process is mediated in large part by osteoblast... (Review)
Review
Interaction between endothelial cells and osteoblasts is essential for bone development and homeostasis. This process is mediated in large part by osteoblast angiotropism, the migration of osteoblasts alongside blood vessels, which is crucial for the homing of osteoblasts to sites of bone formation during embryogenesis and in mature bones during remodeling and repair. Specialized bone endothelial cells that form "type H" capillaries have emerged as key interaction partners of osteoblasts, regulating osteoblast differentiation and maturation and ensuring their migration towards newly forming trabecular bone areas. Recent revolutions in high-resolution imaging methodologies for bone as well as single cell and RNA sequencing technologies have enabled the identification of some of the signaling pathways and molecular interactions that underpin this regulatory relationship. Similarly, the intercellular cross talk between endothelial cells and entombed osteocytes that is essential for bone formation, repair, and maintenance are beginning to be uncovered. This is a relatively new area of research that has, until recently, been hampered by a lack of appropriate analysis tools. Now that these tools are available, greater understanding of the molecular relationships between these key cell types is expected to facilitate identification of new drug targets for diseases of bone formation and remodeling.
Topics: Animals; Bone Development; Bone Remodeling; Bone and Bones; Endothelial Cells; Homeostasis; Humans; Osteoblasts; Osteogenesis; Signal Transduction
PubMed: 34298886
DOI: 10.3390/ijms22147253