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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 -
Frontiers in Endocrinology 2020Excess adiposity in childhood may affect bone development, ultimately leading to bone frailty. Previous reports showing an increased rate of extremity fractures in... (Review)
Review
Excess adiposity in childhood may affect bone development, ultimately leading to bone frailty. Previous reports showing an increased rate of extremity fractures in children with obesity support this fear. On the other hand, there is also evidence suggesting that bone mineral content is higher in obese children than in normal weight peers. Both adipocytes and osteoblasts derive from multipotent mesenchymal stem cells (MSCs) and obesity drives the differentiation of MSCs toward adipocytes at the expense of osteoblast differentiation. Furthermore, adipocytes in bone marrow microenvironment release a number of pro-inflammatory and immunomodulatory molecules that up-regulate formation and activation of osteoclasts, thus favoring bone frailty. On the other hand, body adiposity represents a mechanical load, which is beneficial for bone accrual. In this frame, bone quality, and structure result from the balance of inflammatory and mechanical stimuli. Diet, physical activity and the hormonal milieu at puberty play a pivotal role on this balance. In this review, we will address the question whether the bone of obese children and adolescents is unhealthy in comparison with normal-weight peers and discuss mechanisms underlying the differences in bone quality and structure. We anticipate that many biases and confounders affect the clinical studies conducted so far and preclude us from achieving robust conclusions. Sample-size, lack of adequate controls, heterogeneity of study designs are the major drawbacks of the existing reports. Due to the increased body size of children with obesity, dual energy absorptiometry might overestimate bone mineral density in these individuals. Magnetic resonance imaging, peripheral quantitative CT (pQCT) scanning and high-resolution pQCT are promising techniques for the accurate estimate of bone mineral content in obese children. Moreover, no longitudinal study on the risk of incident osteoporosis in early adulthood of children and adolescents with obesity is available. Finally, we will address emerging dietary issues (i.e., the likely benefits for the bone health of polyunsaturated fatty acids and polyphenols) since an healthy diet (i.e., the Mediterranean diet) with balanced intake of certain nutrients associated with physical activity remain the cornerstones for achieving an adequate bone accrual in young individuals regardless of their adiposity degree.
Topics: Adolescent; Bone Density; Bone Development; Bone and Bones; Child; Exercise; Humans; Osteoporosis; Pediatric Obesity; Puberty
PubMed: 32390939
DOI: 10.3389/fendo.2020.00200 -
The Journal of Clinical Investigation Feb 2016Osteoblast-derived VEGF is important for bone development and postnatal bone homeostasis. Previous studies have demonstrated that VEGF affects bone repair and...
Osteoblast-derived VEGF is important for bone development and postnatal bone homeostasis. Previous studies have demonstrated that VEGF affects bone repair and regeneration; however, the cellular mechanisms by which it works are not fully understood. In this study, we investigated the functions of osteoblast-derived VEGF in healing of a bone defect. The results indicate that osteoblast-derived VEGF plays critical roles at several stages in the repair process. Using transgenic mice with osteoblast-specific deletion of Vegfa, we demonstrated that VEGF promoted macrophage recruitment and angiogenic responses in the inflammation phase, and optimal levels of VEGF were required for coupling of angiogenesis and osteogenesis in areas where repair occurs by intramembranous ossification. VEGF likely functions as a paracrine factor in this process because deletion of Vegfr2 in osteoblastic lineage cells enhanced osteoblastic maturation and mineralization. Furthermore, osteoblast- and hypertrophic chondrocyte-derived VEGF stimulated recruitment of blood vessels and osteoclasts and promoted cartilage resorption at the repair site during the periosteal endochondral ossification stage. Finally, osteoblast-derived VEGF stimulated osteoclast formation in the final remodeling phase of the repair process. These findings provide a basis for clinical strategies to improve bone regeneration and treat defects in bone healing.
Topics: Animals; Bone Regeneration; Calcification, Physiologic; Cell Differentiation; Mice; Mice, Knockout; Osteoblasts; Osteogenesis; Vascular Endothelial Growth Factor A
PubMed: 26731472
DOI: 10.1172/JCI82585 -
Biomedical and Environmental Sciences :... Jan 2015
Review
Topics: Animals; Biomechanical Phenomena; Bone Development; Bone Remodeling; Bone and Bones; Fracture Healing; Fractures, Bone
PubMed: 25566863
DOI: 10.3967/bes2015.006 -
ELife Mar 2020Mechanical forces are fundamental regulators of cell behaviors. However, molecular regulation of mechanotransduction remain poorly understood. Here, we identified the...
Mechanical forces are fundamental regulators of cell behaviors. However, molecular regulation of mechanotransduction remain poorly understood. Here, we identified the mechanosensitive channels Piezo1 and Piezo2 as key force sensors required for bone development and osteoblast differentiation. Loss of Piezo1, or more severely Piezo1/2, in mesenchymal or osteoblast progenitor cells, led to multiple spontaneous bone fractures in newborn mice due to inhibition of osteoblast differentiation and increased bone resorption. In addition, loss of Piezo1/2 rendered resistant to further bone loss caused by unloading in both bone development and homeostasis. Mechanistically, Piezo1/2 relayed fluid shear stress and extracellular matrix stiffness signals to activate Ca influx to stimulate Calcineurin, which promotes concerted activation of NFATc1, YAP1 and ß-catenin transcription factors by inducing their dephosphorylation as well as NFAT/YAP1/ß-catenin complex formation. Yap1 and ß-catenin activities were reduced in the Piezo1 and Piezo1/2 mutant bones and such defects were partially rescued by enhanced ß-catenin activities.
Topics: Adaptor Proteins, Signal Transducing; Animals; Bone Development; Bone Marrow Cells; Cell Cycle Proteins; Extremities; Gene Expression Regulation, Developmental; Ion Channels; Mechanotransduction, Cellular; Mice; Mice, Knockout; NFATC Transcription Factors; Stromal Cells; Tissue Culture Techniques; YAP-Signaling Proteins; beta Catenin
PubMed: 32186512
DOI: 10.7554/eLife.52779 -
Nutrients Mar 2019Calcium is an important nutrient with impact upon many biological systems, most notably bone. Ensuring adequate calcium intake throughout the lifespan is essential to... (Review)
Review
Calcium is an important nutrient with impact upon many biological systems, most notably bone. Ensuring adequate calcium intake throughout the lifespan is essential to building and maintaining bone. Lactose intolerance may predispose individuals to low calcium intake as the number of lactose-free, calcium-rich food sources is limited. In this review, we summarize data from human and animal studies on the influence of lactose and lactase deficiency on calcium absorption and bone health. Based on the available evidence, neither dietary lactose nor lactase deficiency have a significant impact on calcium absorption in adult humans. However, lactose intolerance may lead to reduced bone density and fragility fractures when accompanied by decreased intake or avoidance of dairy. Recently published human trials and meta-analyses suggest a weak but significant association between dairy consumption and bone health, particularly in children. Given the availability of simple dietary approaches to building lactose tolerance and the nutritional deficiencies associated with dairy avoidance, multiple public health organizations recommend that all individuals-including those that are lactose intolerant-consume three servings of dairy per day to ensure adequate nutrient intakes and optimal bone health.
Topics: Aging; Bone Density; Bone Development; Calcium; Humans; Lactose Intolerance
PubMed: 30925689
DOI: 10.3390/nu11040718 -
Proceedings of the National Academy of... Nov 2016Appreciation of the role of the gut microbiome in regulating vertebrate metabolism has exploded recently. However, the effects of gut microbiota on skeletal growth and...
Appreciation of the role of the gut microbiome in regulating vertebrate metabolism has exploded recently. However, the effects of gut microbiota on skeletal growth and homeostasis have only recently begun to be explored. Here, we report that colonization of sexually mature germ-free (GF) mice with conventional specific pathogen-free (SPF) gut microbiota increases both bone formation and resorption, with the net effect of colonization varying with the duration of colonization. Although colonization of adult mice acutely reduces bone mass, in long-term colonized mice, an increase in bone formation and growth plate activity predominates, resulting in equalization of bone mass and increased longitudinal and radial bone growth. Serum levels of insulin-like growth factor 1 (IGF-1), a hormone with known actions on skeletal growth, are substantially increased in response to microbial colonization, with significant increases in liver and adipose tissue IGF-1 production. Antibiotic treatment of conventional mice, in contrast, decreases serum IGF-1 and inhibits bone formation. Supplementation of antibiotic-treated mice with short-chain fatty acids (SCFAs), products of microbial metabolism, restores IGF-1 and bone mass to levels seen in nonantibiotic-treated mice. Thus, SCFA production may be one mechanism by which microbiota increase serum IGF-1. Our study demonstrates that gut microbiota provide a net anabolic stimulus to the skeleton, which is likely mediated by IGF-1. Manipulation of the microbiome or its metabolites may afford opportunities to optimize bone health and growth.
Topics: Adipose Tissue; Animals; Bone Development; Bone and Bones; Fatty Acids, Volatile; Female; Gastrointestinal Microbiome; Insulin-Like Growth Factor I; Liver; Male; Mice; Osteogenesis; Specific Pathogen-Free Organisms
PubMed: 27821775
DOI: 10.1073/pnas.1607235113 -
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... May 2023Bone is an important tissue which is a structural body component, carrying out the roles of mechanical stress response and organ/tissue protection [...].
Bone is an important tissue which is a structural body component, carrying out the roles of mechanical stress response and organ/tissue protection [...].
Topics: Bone Regeneration; Bone Development; Bone and Bones; Stress, Mechanical; Tissue Engineering; Tissue Scaffolds
PubMed: 37240107
DOI: 10.3390/ijms24108761