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The Journal of Physiological Sciences :... Jul 2012Endochondral bone growth in young growing mammals or adult mammals with persistent growth plates progresses from proliferation, maturation and hypertrophy of growth... (Review)
Review
Endochondral bone growth in young growing mammals or adult mammals with persistent growth plates progresses from proliferation, maturation and hypertrophy of growth plate chondrocytes to mineralization of cartilaginous matrix to form an osseous tissue. This complex process is tightly regulated by a number of factors with different impacts, such as genetics, endocrine/paracrine factors [e.g., PTHrP, 1,25(OH)(2)D(3), IGF-1, FGFs, and prolactin], and nutritional status (e.g., dietary calcium and vitamin D). Despite a strong link between growth plate function and elongation of the long bone, little is known whether endochondral bone growth indeed determines bone calcium accretion, bone mineral density (BMD), and/or peak bone mass. Since the process ends with cartilaginous matrix calcification, an increase in endochondral bone growth typically leads to more calcium accretion in the primary spongiosa and thus higher BMD. However, in lactating rats with enhanced trabecular bone resorption, bone elongation is inversely correlated with BMD. Although BMD can be increased by factors that enhance endochondral bone growth, the endochondral bone growth itself is unlikely to be an important determinant of peak bone mass since it is strongly determined by genetics. Therefore, endochondral bone growth and bone elongation are associated with calcium accretion only in a particular subregion of the long bone, but do not necessarily predict BMD and peak bone mass.
Topics: Animals; Bone Density; Bone Development; Calcification, Physiologic; Calcium; Cartilage; Female; Growth Plate; Lactation; Pregnancy
PubMed: 22627708
DOI: 10.1007/s12576-012-0212-0 -
International Journal of Molecular... Sep 2021Bone fragility is a pathological condition caused by altered homeostasis of the mineralized bone mass with deterioration of the microarchitecture of the bone tissue,... (Review)
Review
Bone fragility is a pathological condition caused by altered homeostasis of the mineralized bone mass with deterioration of the microarchitecture of the bone tissue, which results in a reduction of bone strength and an increased risk of fracture, even in the absence of high-impact trauma. The most common cause of bone fragility is primary osteoporosis in the elderly. However, bone fragility can manifest at any age, within the context of a wide spectrum of congenital rare bone metabolic diseases in which the inherited genetic defect alters correct bone modeling and remodeling at different points and aspects of bone synthesis and/or bone resorption, leading to defective bone tissue highly prone to long bone bowing, stress fractures and pseudofractures, and/or fragility fractures. To date, over 100 different Mendelian-inherited metabolic bone disorders have been identified and included in the OMIM database, associated with germinal heterozygote, compound heterozygote, or homozygote mutations, affecting over 80 different genes involved in the regulation of bone and mineral metabolism. This manuscript reviews clinical bone phenotypes, and the associated bone fragility in rare congenital metabolic bone disorders, following a disease taxonomic classification based on deranged bone metabolic activity.
Topics: Bone Density; Bone Development; Bone Diseases, Metabolic; Bone Remodeling; Bone Resorption; Calcification, Physiologic; Extracellular Matrix Proteins; Fractures, Bone; Humans; Metabolic Networks and Pathways; Mutation; Signal Transduction
PubMed: 34638624
DOI: 10.3390/ijms221910281 -
Frontiers in Bioscience (Landmark... Jun 2011The primary focus of this article is to review intramembranous bone development, that is, ossification that takes place directly. Comparisons with endochondral... (Review)
Review
The primary focus of this article is to review intramembranous bone development, that is, ossification that takes place directly. Comparisons with endochondral ossification (ossification with a cartilage precursor) will be made in order to illustrate the differences between these two modes of ossification and to highlight the comparatively sparse information that is available about intramembranous ossification. Despite decades of research into understanding skeletal development, there is still much to learn. Most of the research in this area has focused on the development of the calvariae (or skull bones) as typical intramembranous bones and the development of the limb bones as a typical endochondral bones. Few studies investigate other skeletal elements or compare these processes in a systematic manner. In this review, I focus primarily on condensation formation and skeletal patterning with specific examples from different organisms.
Topics: Animals; Body Patterning; Bone Development; Bone Morphogenetic Proteins; Core Binding Factor Alpha 1 Subunit; Fibroblast Growth Factors; Hedgehog Proteins; Homeodomain Proteins; Humans; MSX1 Transcription Factor; Osteogenesis; SOX9 Transcription Factor; Signal Transduction; Wnt Proteins
PubMed: 21622205
DOI: 10.2741/3882 -
Zoological Research May 2021Intermuscular bones (IBs) are slender linear bones embedded in muscle, which ossify from tendons through a process of intramembranous ossification, and only exist in... (Review)
Review
Intermuscular bones (IBs) are slender linear bones embedded in muscle, which ossify from tendons through a process of intramembranous ossification, and only exist in basal teleosts. IBs are essential for fish swimming, but they present a choking risk during human consumption, especially in children, which can lead to commercial risks that have a negative impact on the aquaculture of these fish. In this review, we discuss the morphogenesis and functions of IBs, including their underlying molecular mechanisms, as well as the advantages and disadvantages of different methods for IB studies and techniques for breeding and generating IB-free fish lines. This review reveals that the many key genes involved in tendon development, osteoblast differentiation, and bone formation, e.g., , , , , , and , also play roles in IB development. Thus, this paper provides useful information for the breeding of new fish strains without IBs via genome editing and artificial selection.
Topics: Animals; Aquaculture; Bone Development; Diet; Fishes
PubMed: 33998184
DOI: 10.24272/j.issn.2095-8137.2021.044 -
Journal of Bone and Mineral Research :... Dec 1992The role of in vivo mechanical loading histories in normal skeletogenesis is related to the process of adaptive, stress-regulated bone remodeling in the adult. The... (Review)
Review
The role of in vivo mechanical loading histories in normal skeletogenesis is related to the process of adaptive, stress-regulated bone remodeling in the adult. The results of many previous computer models for endochondral ossification and bone modeling and remodeling are reviewed. These studies support the view that simple stress-related mathematical algorithms or "construction rules" can be used to emulate normal skeletal development and architectural construction. Such mathematical rules presumably represent the net result of biophysical phenomena influencing cell metabolism and biosynthetic activity. These rules are also successful in describing the adaptation of adult bone to changes in tissue stresses. The findings suggest that stress-related functional adaptation in mature bones may be merely the adult manifestation of the same mechanical construction rules that guide and constrain normal development.
Topics: Adaptation, Physiological; Biomechanical Phenomena; Bone Density; Bone Development; Bone Remodeling; Computer Simulation; Femur; Humans; Osteogenesis; Stress, Mechanical
PubMed: 1485546
DOI: 10.1002/jbmr.5650071405 -
Blood Jan 2009Wnt/beta-catenin signaling is central to bone development and homeostasis in adulthood and its deregulation is associated with bone pathologies. Dickkopf-1 (DKK1), a... (Review)
Review
Wnt/beta-catenin signaling is central to bone development and homeostasis in adulthood and its deregulation is associated with bone pathologies. Dickkopf-1 (DKK1), a soluble inhibitor of Wnt/beta-catenin signaling required for embryonic head development, regulates Wnt signaling by binding to the Wnt coreceptor lipoprotein-related protein-5 (LRP5)/Arrow. LRP5 mutations causing high bone mass syndromes disrupt DKK1-mediated regulation of LRP5. Forced overexpression of Dkk1 in osteoblasts causes osteopenia, disruption of the hematopoietic stem cell (HSC) niche, and defects in HSC function. Dkk1 also inhibits fracture repair. Studies suggest that DKK1 activation in osteoblasts is the underlying cause of glucocorticoid- and estrogen deficiency-mediated osteoporosis, and at least partially underlies the teratogenic effects of thalidomide on limb development. DKK1 induces proliferation of mesenchymal stem cells (MSC) in vitro and may play a role in the development of high-grade undifferentiated pleomorphic sarcomas derived from MSC and osteosarcomas. DKK1 has been implicated in causing erosive arthritis, the osteolytic phenotypes of multiple myeloma and metastatic breast cancer, and osteoblastic metastases of prostate cancer. Preclinical studies have shown that neutralizing DKK1/Dkk1 and/or enhancing Wnt/beta-catenin signaling may prove effective in treating bone pathologies. Here, we review the rapidly growing body of literature defining a pivotal role for DKK1 in bone health and disease.
Topics: Animals; Bone Development; Bone Diseases; Bone and Bones; Homeostasis; Humans; Intercellular Signaling Peptides and Proteins
PubMed: 18687985
DOI: 10.1182/blood-2008-03-145169 -
Development (Cambridge, England) Dec 2017During embryogenesis, the musculoskeletal system develops while containing within itself a force generator in the form of the musculature. This generator becomes... (Review)
Review
During embryogenesis, the musculoskeletal system develops while containing within itself a force generator in the form of the musculature. This generator becomes functional relatively early in development, exerting an increasing mechanical load on neighboring tissues as development proceeds. A growing body of evidence indicates that such mechanical forces can be translated into signals that combine with the genetic program of organogenesis. This unique situation presents both a major challenge and an opportunity to the other tissues of the musculoskeletal system, namely bones, joints, tendons, ligaments and the tissues connecting them. Here, we summarize the involvement of muscle-induced mechanical forces in the development of various vertebrate musculoskeletal components and their integration into one functional unit.
Topics: Animals; Biomechanical Phenomena; Bone Development; Chondrogenesis; Humans; Mice; Models, Biological; Muscle Development; Musculoskeletal Development; Signal Transduction
PubMed: 29183940
DOI: 10.1242/dev.151266 -
Zoology (Jena, Germany) Oct 2017The presence of regional variation in the osteogenic abilities of cranial bones underscores the fact that the mechanobiology of the mammalian skull is more complex than...
The presence of regional variation in the osteogenic abilities of cranial bones underscores the fact that the mechanobiology of the mammalian skull is more complex than previously recognized. However, the relationship between patterns of cranial bone formation and biomineralization remains incompletely understood. In four strains of mice, micro-computed tomography was used to measure tissue mineral density during perinatal development in three skull regions (calvarium, basicranium, mandible) noted for variation in loading environment, embryological origin, and ossification mode. Biomineralization levels increased during perinatal ontogeny in the mandible and calvarium, but did not increase in the basicranium. Tissue mineral density levels also varied intracranially, with density in the mandible being highest, in the basicranium intermediate, and in the calvarium lowest. Perinatal increases in, and elevated levels of, mandibular biomineralization appear related to the impending postweaning need to resist elevated masticatory stresses. Similarly, perinatal increases in calvarial biomineralization may be linked to ongoing brain expansion, which is known to stimulate sutural bone formation in this region. The lack of perinatal increase in basicranial biomineralization could be a result of earlier developmental maturity in the cranial base relative to other skull regions due to its role in supporting the brain's mass throughout ontogeny. These results suggest that biomineralization levels and age-related trajectories throughout the skull are influenced by the functional environment and ontogenetic processes affecting each region, e.g., onset of masticatory loads in the mandible, whereas variation in embryology and ossification mode may only have secondary effects on patterns of biomineralization. Knowledge of perinatal variation in tissue mineral density, and of normal cranial bone formation early in development, may benefit clinical therapies aiming to correct developmental defects and traumatic injuries in the skull, and more generally characterize loading environments and skeletal adaptations in mammals by highlighting the need for multi-level analyses for evaluating functional performance of cranial bone.
Topics: Adaptation, Physiological; Aging; Animals; Animals, Newborn; Bone Development; Calcification, Physiologic; Mandible; Mice; Skull
PubMed: 28807504
DOI: 10.1016/j.zool.2017.01.002 -
Lymphology 2020Ectopic lymphatics form in bone and promote bone destruction in diseases such as Gorham-Stout disease, generalized lymphatic anomaly, and kaposiform lymphangiomatosis....
Ectopic lymphatics form in bone and promote bone destruction in diseases such as Gorham-Stout disease, generalized lymphatic anomaly, and kaposiform lymphangiomatosis. However, the role lymphatics serve in normal bone development and repair is poorly understood. The objective of this study was to characterize bone development and fracture healing in mice that have a defect in the development of the lymphatic vasculature. We found that bones in wild-type adult mice and mouse embryos did not have lymphatics. We also found that bone development was normal in Vegfr3 (Chy/Chy) embryos. These mice do not have lymphatics and die shortly after birth. To determine whether lymphatics serve a role in postnatal bone development and fracture healing, we analyzed bones from Vegfr3 (wt/Chy) mice. These mice are viable and have fewer lymphatics than wild-type mice. We found that postnatal bone development and fracture healing was normal in Vegfr3 (wt/Chy) mice. Taken together, our results suggest that lymphatics do not play a major role in normal bone development or repair.
Topics: Animals; Bone Development; Bone and Bones; Fracture Healing; Lymphangiogenesis; Lymphatic Vessels; Mice
PubMed: 33721923
DOI: No ID Found -
Frontiers in Endocrinology 2020Osteoporosis is a significant cause of morbidity and mortality in contemporary populations. This common disease of aging results from a state of bone fragility that... (Review)
Review
Osteoporosis is a significant cause of morbidity and mortality in contemporary populations. This common disease of aging results from a state of bone fragility that occurs with low bone mass and loss of bone quality. Osteoporosis is thought to have origins in childhood. During growth and development, there are rapid gains in bone dimensions, mass, and strength. Peak bone mass is attained in young adulthood, well after the cessation of linear growth, and is a major determinant of osteoporosis later in life. Here we discuss the evolutionary implications of osteoporosis as a disease with developmental origins that is shaped by the interaction among genes, behavior, health status, and the environment during the attainment of peak bone mass. Studies of contemporary populations show that growth, body composition, sexual maturation, physical activity, nutritional status, and dietary intake are determinants of childhood bone accretion, and provide context for interpreting bone strength and osteoporosis in skeletal populations. Studies of skeletal populations demonstrate the role of subsistence strategies, social context, and occupation in the development of skeletal strength. Comparisons of contemporary living populations and archeological skeletal populations suggest declines in bone density and strength that have been occurring since the Pleistocene. Aspects of western lifestyles carry implications for optimal peak bone mass attainment and lifelong skeletal health, from increased longevity to circumstances during development such as obesity and sedentism. In light of these considerations, osteoporosis is a disease of contemporary human evolution and evolutionary perspectives provide a key lens for interpreting the changing global patterns of osteoporosis in human health.
Topics: Adult; Aged; Aging; Biological Evolution; Bone Density; Bone Development; Bone and Bones; Child; Exercise; Health; Humans; Life Style; Young Adult
PubMed: 32194504
DOI: 10.3389/fendo.2020.00099