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International Journal of Biological... 2021Fibroblast growth factors (FGFs) include a large family of growth factors that play a critical role in maintaining bone homeostasis, but the specific role of its members...
Fibroblast growth factors (FGFs) include a large family of growth factors that play a critical role in maintaining bone homeostasis, but the specific role of its members such as FGF7 does not well understand. Osteoblasts are a kind of major cells essential for bone formation. Osteoblasts interact with one another to create the unique structure of osteons. The well-connected osteons constitute the cortical bone. As an early osteocyte marker that triggers actin cytoskeleton dynamics, E11 is essential for osteoblasts' dendrites formation. However, the upstream which regulates E11 is mainly unknown. The purpose of this study was to examine the influence of FGF7 on the expression and the distribution of E11 in osteoblasts, which mediated osteoblasts' processes formation and gap junctional intercellular communication (GJIC) partly through connexin43 (Cx43). We first demonstrated that FGF7 increased the expression of E11 in osteoblasts. We then showed that FGF7 promoted osteoblasts' dendrites elongation and functional gap junctions formation. Furthermore, E11 interacted directly with Cx43 in primary osteoblasts. MAPK pathway and PI3K-AKT pathway were involved in the effect of FGF7. Our results shed light on the unique role of FGF7 on osteoblasts, which may indicate that FGF7 plays a more significant role in the later stages of bone development and homeostasis.
Topics: 3T3 Cells; Animals; Cell Communication; Connexin 43; Fibroblast Growth Factor 7; Ligands; MAP Kinase Signaling System; Membrane Glycoproteins; Mice; Osteoblasts
PubMed: 34671204
DOI: 10.7150/ijbs.65240 -
Wiadomosci Lekarskie (Warsaw, Poland :... 2021The aim: To evaluate morphological changes in long tubular bones of mature rats under the influence of experimental hyperglycemia.
OBJECTIVE
The aim: To evaluate morphological changes in long tubular bones of mature rats under the influence of experimental hyperglycemia.
PATIENTS AND METHODS
Materials and methods: The study was conducted on 140 nonlinear white male rats divided into two groups. The experimental group included rats that were introduced into a state of hyperglycemia by a single intraperitoneal injection of an alloxan dihydrate solution at a dose of 150 mg / kg body weight in 0.9% sodium chloride. The control group included rats that were injected with a similar volume of 0.9% sodium chloride one time intraperitoneally. The animals were taken out of the experiment on the 2nd, 30th, 60th, 90th, 120th, 150th and 180th day. Right and left femur and humerus were studied by morphometric and histological methods.
RESULTS
Results: Under conditions of prolonged uncontrolled hyperglycemia in mature rats, there is a slowdown in the growth rate of length and thickness of femur and humerus. This is indicated by a significant decrease in the length of bone and its diaphyses, as well as by a decrease in the cross-sectional area of the diaphysis, the width of the proximal and distal epiphyses, starting from 120 and 90 days of the experiment, respectively. The relative area of trabecular tissue, thickness of trabeculae and epiphyseal cartilage decreases in comparison with animals of the control group. The diameter of osteons and their channels increases in cortical tissue. Changes in the microarchitecture of the trabecular and cortical compartments of femur and humerus under conditions of hyperglycemia are similar and are characterized by a reduced bone mass, bone disorder progression and remodeling disorders.
CONCLUSION
Conclusions: Prolonged uncontrolled experimental hyperglycemia leads to slow growth of femur and humerus in mature rats, which is accompanied by an increase in microarchitecture disorder of the trabecular and cortical compartments, causing miniaturization of bones and, consequently, violation of their biomechanical properties and increased risk of fractures.
Topics: Animals; Bone Density; Bone and Bones; Femur; Fractures, Bone; Hyperglycemia; Male
PubMed: 34725275
DOI: No ID Found -
The Journals of Gerontology. Series A,... Oct 2013Mice are increasingly used for investigation of the pathophysiology of osteoporosis because their genome is easily manipulated, and their skeleton is similar to that of... (Review)
Review
Mice are increasingly used for investigation of the pathophysiology of osteoporosis because their genome is easily manipulated, and their skeleton is similar to that of humans. Unlike the human skeleton, however, the murine skeleton continues to grow slowly after puberty and lacks osteonal remodeling of cortical bone. Yet, like humans, mice exhibit loss of cancellous bone, thinning of cortical bone, and increased cortical porosity with advancing age. Histologic evidence in mice and humans alike indicates that inadequate osteoblast-mediated refilling of resorption cavities created during bone remodeling is responsible. Mouse models of progeria also show bone loss and skeletal defects associated with senescence of early osteoblast progenitors. Additionally, mouse models of atherosclerosis, which often occurs in osteoporotic participants, also suffer bone loss, suggesting that common diseases of aging share pathophysiological pathways. Knowledge of the causes of skeletal fragility in mice should therefore be applicable to humans if inherent limitations are recognized.
Topics: Aging, Premature; Animals; Atherosclerosis; Bone Density; Disease Models, Animal; Humans; Mice; Osteoporosis; Species Specificity
PubMed: 23689830
DOI: 10.1093/gerona/glt046 -
BioMed Research International 2022This study was conducted to better understand the specific behavior of the intraosseous fluid flow. We calculated the number and distribution of bone canaliculi around...
This study was conducted to better understand the specific behavior of the intraosseous fluid flow. We calculated the number and distribution of bone canaliculi around the osteocytes based on the varying shapes of osteocytes. We then used these calculated parameters and other bone microstructure data to estimate the anisotropy permeability of the lacunar-canalicular network. Poroelastic finite element models of the osteon were established, and the influence of the osteocyte shape on the fluid flow properties of osteons under an axial displacement load was analyzed. Two types of boundary conditions (BC) that might occur in physiological environments were considered on the cement line of the osteon. BC1 allows free fluid passage from the outer elastic restraint boundary, and BC2 is impermeable and allows no free fluid passage from outer displacement constrained boundary. They both have the same inner boundary conditions that allow fluid to pass through. Changes in the osteocyte shape altered the maximum value of pressure gradient (PG), pore pressure (PP), fluid velocity (FV), and fluid shear stress (FSS) relative to the reference model (spherical osteocytes). The maximum PG, PP, FV, and FSS in BC2 were nearly 100% larger than those in BC1, respectively. It is found that the BC1 was closer to the real physiological environment. The fluid flow along different directions in the elongated osteocyte model was more evident than that in other models, which may have been due to the large difference in permeability along different directions. Changes in osteocyte shape significantly affect the degrees of anisotropy of fluid flow and porous media of the osteon. The model presented in this study can accurately quantify fluid flow in the lacunar-canalicular network.
Topics: Bone and Bones; Haversian System; Osteocytes; Porosity; Stress, Mechanical
PubMed: 35677099
DOI: 10.1155/2022/3935803 -
Journal of Anatomy Jun 2021Lacking fur, living in eusocial colonies and having the longest lifespan of any rodent, makes naked mole-rats (NMRs) rather peculiar mammals. Although they exhibit a...
Lacking fur, living in eusocial colonies and having the longest lifespan of any rodent, makes naked mole-rats (NMRs) rather peculiar mammals. Although they exhibit a high degree of polymorphism, skeletal plasticity and are considered a novel model to assess the effects of delayed puberty on the skeletal system, scarce information on their morphogenesis exists. Here, we examined a large ontogenetic sample (n = 76) of subordinate individuals to assess the pattern of bone growth and bone microstructure of fore- and hindlimb bones by using histomorphological techniques. Over 290 undecalcified thin cross-sections from the midshaft of the humerus, ulna, femur, and tibia from pups, juveniles and adults were analyzed with polarized light microscopy. Similar to other fossorial mammals, NMRs exhibited a systematic cortical thickening of their long bones, which clearly indicates a conserved functional adaptation to withstand the mechanical strains imposed during digging, regardless of their chisel-tooth predominance. We describe a high histodiversity of bone matrices and the formation of secondary osteons in NMRs. The bones of pups are extremely thin-walled and grow by periosteal bone formation coupled with considerable expansion of the medullary cavity, a process probably tightly regulated and adapted to optimize the amount of minerals destined for skeletal development, to thus allow the female breeder to produce a higher number of pups, as well as several litters. Subsequent cortical thickening in juveniles involves high amounts of endosteal bone apposition, which contrasts with the bone modeling of other mammals where a periosteal predominance exists. Adults have bone matrices predominantly consisting of parallel-fibered bone and lamellar bone, which indicate intermediate to slow rates of osteogenesis, as well as the development of poorly vascularized lamellar-zonal tissues separated by lines of arrested growth (LAGs) and annuli. These features reflect the low metabolism, low body temperature and slow growth rates reported for this species, as well as indicate a cyclical pattern of osteogenesis. The presence of LAGs in captive individuals was striking and indicates that postnatal osteogenesis and its consequent cortical stratification most likely represents a plesiomorphic thermometabolic strategy among endotherms which has been suggested to be regulated by endogenous rhythms. However, the generalized presence of LAGs in this and other subterranean taxa in the wild, as well as recent investigations on variability of environmental conditions in burrow systems, supports the hypothesis that underground environments experience seasonal fluctuations that may influence the postnatal osteogenesis of animals by limiting the extension of burrow systems during the unfavorable dry seasons and therefore the finding of food resources. Additionally, the intraspecific variation found in the formation of bone tissue matrices and vascularization suggested a high degree of developmental plasticity in NMRs, which may help explaining the polymorphism reported for this species. The results obtained here represent a valuable contribution to understanding the relationship of several aspects involved in the morphogenesis of the skeletal system of a mammal with extraordinary adaptations.
Topics: Animals; Bone Development; Femur; Humerus; Mole Rats; Osteogenesis; Tibia; Ulna
PubMed: 33305850
DOI: 10.1111/joa.13381 -
Journal of Biomedical Materials... Oct 2018Unidirectional porous hydroxyapatite (UDPHAp) bone substitute comprises a microstructure of cross-sectionally oval pores with diameters ranging from 30 to 300 µm. Bone...
Unidirectional porous hydroxyapatite (UDPHAp) bone substitute comprises a microstructure of cross-sectionally oval pores with diameters ranging from 30 to 300 µm. Bone remodeling within the UDPHAp is expected upon implantation into bone; however, the mechanism and factors influencing this bone growth remain unclear. The objectives of the present study were to assess the vasculature and microstructure of newly formed bone and to determine how bone formation is affected by load transfer and UDPHAp pore size. Formation of osteon-like structures, defined by the presence of lacunae, canaliculi and a central lumen containing capillaries, was observed within the implanted UDPHAp material in all animals after six weeks. The number of osteocytes and osteon-like structures in areas adjacent to the cortex of recipient bone was significantly higher than in areas next to the medullary cavity throughout the recovery period. Notably, osteon-like structures tended to form in smaller diameter pores. Continuous bone remodeling might be promoted by the rapid formation of unidirectional capillaries and the osteocyte lacunae-canalicular system. Load transfer and smaller pore size could positively affect cortical bone regeneration. © 2018 The Authors Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2665-2672, 2018.
Topics: Animals; Bone Regeneration; Bone Substitutes; Durapatite; Osteocytes; Osteogenesis; Porosity; Rabbits
PubMed: 29437284
DOI: 10.1002/jbm.b.34083 -
Journal of Biomechanics Jan 2013Cortical bone has a hierarchical structure, spanning from the macrostructure at several millimeters or whole bone level, the microstructure at several hundred...
Cortical bone has a hierarchical structure, spanning from the macrostructure at several millimeters or whole bone level, the microstructure at several hundred micrometers level, to the nanostructure at hydroxyapatite (HAp) crystals and collagen fibrils levels. The aim of the study is to understand the relationship between the HAp crystal orientation and the elastic modulus and the relationship between the osteon area fraction and the deformation behavior of HAp crystals in cortical bone. In the experiments, five strip specimens (40×2×1mm(3)) aligned with the bone axis were taken from the cortical bone of a bovine femur. The degree of c-axis orientation of HAp crystals in the specimens was measured with the X-ray diffraction technique with the imaging plate. To measure the deformation behavior of HAp crystals in the specimens, tensile tests under X-ray irradiation were conducted. The specimens were cut at the X-ray measurement positions and osteon area fraction and porosity at the transverse cross-sections were observed. Further, the volume fraction of HAp of the specimens was measured. Results showed the degree of c-axis orientation of HAp crystals was positively correlated with the elastic modulus of the specimens (r=0.94). The volume fraction of HAp and the porosity showed no statistical correlation with the elastic modulus and the tensile strength. The HAp crystal strain ε(H) increased linearly with the bone tissue strain ε. The average value of ε(H)/ε was 0.69±0.13 and there was no correlation between the osteon area fraction and ε(H)/ε (r=-0.27, p=0.33). The results suggest that the degree of c-axis orientation of HAp crystals affects the elastic modulus and the magnitude of HAp crystal strain does not depend on the osteon area fraction.
Topics: Animals; Bone Density; Cattle; Crystallization; Durapatite; Elastic Modulus; Femur; Haversian System; Porosity; Radiography; Tensile Strength
PubMed: 23084783
DOI: 10.1016/j.jbiomech.2012.09.020 -
Bone Reports Jun 2021Diaphyseal long bone cortical tissue from 30 patients with lethal perinatal Sillence II and progressively deforming Sillence III osteogenesis imperfecta (OI) has been...
Histopathology of osteogenesis imperfecta bone. Supramolecular assessment of cells and matrices in the context of woven and lamellar bone formation using light, polarization and ultrastructural microscopy.
Diaphyseal long bone cortical tissue from 30 patients with lethal perinatal Sillence II and progressively deforming Sillence III osteogenesis imperfecta (OI) has been studied at multiple levels of structural resolution. Interpretation in the context of woven to lamellar bone formation by mesenchymal osteoblasts (MOBLs) and surface osteoblasts (SOBLs) respectively demonstrates lamellar on woven bone synthesis as an obligate self-assembly mechanism and bone synthesis following the normal developmental pattern but showing variable delay in maturation caused by structurally abnormal or insufficient amounts of collagen matrix. The more severe the variant of OI is, the greater the persistence of woven bone and the more immature the structural pattern; the pattern shifts to a structurally stronger lamellar arrangement once a threshold accumulation for an adequate scaffold of woven bone has been reached. Woven bone alone characterizes lethal perinatal variants; variable amounts of woven and lamellar bone occur in progressively deforming variants; and lamellar bone increasingly forms rudimentary and then partially compacted osteons not reaching full compaction. At differing levels of microscopic resolution: lamellar bone is characterized by short, obliquely oriented lamellae with a mosaic appearance in progressively deforming forms; polarization defines tissue conformations and localizes initiation of lamellar formation; ultrastructure of bone forming cells shows markedly dilated rough endoplasmic reticulum (RER) and prominent Golgi bodies with disorganized cisternae and swollen dispersed tubules and vesicles, structural indications of storage disorder/stress responses and mitochondrial swelling in cells with massively dilated RER indicating apoptosis; ultrastructural matrix assessments in woven bone show randomly oriented individual fibrils but also short pericellular bundles of parallel oriented fibrils positioned obliquely and oriented randomly to one another and in lamellar bone show unidirectional fibrils that deviate at slight angles to adjacent bundles and obliquely oriented fibril groups consistent with twisted plywood fibril organization. Histomorphometric indices, designed specifically to document woven and lamellar conformations in normal and OI bone, establish ratios for: i) indicating the percentage of an area occupied by cells (cellularity index) and ii) (pericellular matrix domains). Woven bone is more cellular than lamellar bone and OI bone is more cellular than normal bone, but these findings occur in a highly specific fashion with values (high to low) encompassing OI woven, normal woven, OI lamellar and normal lamellar conformations. Conversely, for the ratio, pericellular matrix accumulations in OI woven are smallest and normal lamellar largest. Since genotype-phenotype correlation is not definitive, interposing histologic/structural analysis allowing for a genotype-histopathologic-phenotype correlation will greatly enhance understanding and clinical management of OI.
PubMed: 33665234
DOI: 10.1016/j.bonr.2020.100734 -
Bioactive Materials Jan 2023Calcium phosphates (CaP) represent an important class of osteoconductive and osteoinductive biomaterials. As proof-of-concept, we show how a multi-component CaP...
Calcium phosphates (CaP) represent an important class of osteoconductive and osteoinductive biomaterials. As proof-of-concept, we show how a multi-component CaP formulation (monetite, beta-tricalcium phosphate, and calcium pyrophosphate) guides osteogenesis beyond the physiological envelope. In a sheep model, hollow dome-shaped constructs were placed directly over the occipital bone. At 12 months, large amounts of bone (∼75%) occupy the hollow space with strong evidence of ongoing remodelling. Features of both compact bone (osteonal/osteon-like arrangements) and spongy bone (trabeculae separated by marrow cavities) reveal insights into function/need-driven microstructural adaptation. Pores within the CaP also contain both woven bone and vascularised lamellar bone. Osteoclasts actively contribute to CaP degradation/removal. Of the constituent phases, only calcium pyrophosphate persists within osseous (cutting cones) and non-osseous (macrophages) sites. From a translational perspective, this multi-component CaP opens up exciting new avenues for osteotomy-free and minimally-invasive repair of large bone defects and augmentation of the dental alveolar ridge.
PubMed: 35441115
DOI: 10.1016/j.bioactmat.2022.03.012 -
Journal of Artificial Organs : the... Jun 2021In Japan, where allograft bone transplantation is not widespread, prospects for artificial bones are very high. Therefore, artificial bones with various compositions,... (Review)
Review
In Japan, where allograft bone transplantation is not widespread, prospects for artificial bones are very high. Therefore, artificial bones with various compositions, porous structures, and porosities have been developed and employed for clinical use. Both Affinos and Regenos (made of beta-tricalcium phosphate and hydroxyapatite, respectively) are artificial bones with a unique unidirectional porous structure, in which pores with a diameter suitable for tissue penetration (25-300 μm) are aligned in one direction. The unidirectional porous structure allows rapid penetration of blood deep into the materials by a capillary effect. In animal experiments, Affinos showed well-balanced resorption and was replaced with the host's own bone from an early stage after implantation and new bone formation and remodeling were observed in the cortical bone and medullary cavity. When implanted for clinical situation, resorption from an early stage and good replacement with the patient's own bone were also observed. Regenos has an internal osteon-like material and a vascular-like structure that is maintained within the pores even after long-term implantation, as noted in an animal experiment. When implanted for clinical situation, good osteoconductivity was observed from an early stage of implantation. In addition, the material was observed to be slowly absorbed over time in some cases. We have discussed the beneficial effects of combining teriparatide and platelet-rich plasma impregnation and the potential prospects of these artificial bones.
Topics: Animals; Biocompatible Materials; Bone Regeneration; Bone Substitutes; Bone Transplantation; Calcium Phosphates; Durapatite; Humans; Japan; Porosity; Prostheses and Implants
PubMed: 33893573
DOI: 10.1007/s10047-021-01270-8