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Animal Models and Experimental Medicine Aug 2023Bone microarchitecture is affected by multiple genes, each having a small effect on the external appearance. It is thus challenging to characterize the genes and their...
BACKGROUND
Bone microarchitecture is affected by multiple genes, each having a small effect on the external appearance. It is thus challenging to characterize the genes and their specific effect on bone thickness and porosity. The purpose of this study was to assess the heritability and the genetic variation effect, as well as the sex effect on the calvarial bone thickness (Ca.Th) and calvarial porosity (%PoV) using the Collaborative Cross (CC) mouse population.
METHODS
In the study we examined the parietal bones of 56 mice from 9 lines of CC mice. Morphometric parameters were evaluated using microcomputed tomography (μCT) and included Ca.Th and %PoV. We then evaluated heritability, genetic versus environmental variance and the sex effect for these parameters.
RESULTS
Our morphometric analysis showed that Ca.Th and %PoV are both significantly different among the CC lines with a broad sense heritability of 0.78 and 0.90, respectively. The sex effect within the lines was significant in line IL111 and showed higher values of Ca.Th and %PoV in females compared to males. In line IL19 there was a borderline sex effect in Ca.Th in which males showed higher values than females.
CONCLUSIONS
These results stress the complexity of sex and genotype interactions controlling Ca.Th and %PoV, as the skeletal sexual dimorphism was dependent on the genetic background. This study also shows that the CC population is a powerful tool for establishing the genetic effect on these traits.
Topics: Male; Female; Mice; Animals; Collaborative Cross Mice; X-Ray Microtomography; Bone and Bones; Genotype; Phenotype
PubMed: 37448168
DOI: 10.1002/ame2.12319 -
The Journal of Craniofacial Surgery 2019Over 500,000 bone grafting procedures are performed every year in the United States for neoplastic and traumatic lesions of the craniofacial skeleton, costing $585...
INTRODUCTION
Over 500,000 bone grafting procedures are performed every year in the United States for neoplastic and traumatic lesions of the craniofacial skeleton, costing $585 million in medical care. Current bone grafting procedures are limited, and full-thickness critical-sized defects (CSDs) of the adult human skull thus pose a substantial reconstructive challenge for the craniofacial surgeon. Cell-based strategies have been shown to safely and efficaciously accelerate the rate of bone formation in CSDs in animals. The authors recently demonstrated that supraphysiological transplantation of macrophages seeded in pullalan-collagen composite hydrogels significantly accelerated wound healing in wild type and diabetic mice, an effect mediated in part by enhancing angiogenesis. In this study, the authors investigated the bone healing effects of macrophage transplantation into CSDs of mice.
METHODS
CD1 athymic nude mice (60 days of age) were anesthetized, and unilateral full-thickness critical-sized (4 mm in diameter) cranial defects were created in the right parietal bone, avoiding cranial sutures. Macrophages were isolated from FVB-L2G mice and seeded onto hydroxyapatite-poly (lactic-co-glycolic acid) (HA-PLGA) scaffolds (1.0 × 10 cells per CSD). Scaffolds were incubated for 24 hours before they were placed into the CSDs. Macrophage survival was assessed using three-dimensional in vivo imaging system (3D IVIS)/micro-CT. Micro-CT at 0, 2, 4, 6, and 8 weeks was performed to evaluate gross bone formation, which was quantified using Adobe Photoshop. Microscopic evidence of bone regeneration was assessed at 8 weeks by histology. Bone formation and macrophage survival were compared at each time point using independent samples t tests.
RESULTS
Transplantation of macrophages at supraphysiological concentration had no effect on the formation of bones in CSDs as assessed by either micro-CT data at any time point analyzed (all P > 0.05). These results were corroborated by histology. 3D IVIS/micro-CT demonstrated survival of macrophages through 8 weeks.
CONCLUSION
Supraphysiologic delivery of macrophages to CSDs of mice had no effect on bone formation despite survival of transplanted macrophages through to 8 weeks posttransplantation. Further research into the physiological effects of macrophages on bone regeneration is needed to assess whether recapitulation of these conditions in macrophage-based therapy can promote the healing of large cranial defects.
Topics: Animals; Bone Regeneration; Collagen; Cranial Sutures; Diabetes Mellitus, Experimental; Durapatite; Hydrogels; Macrophages; Mice; Mice, Nude; Osteogenesis; Parietal Bone; Skull; Tissue Scaffolds; X-Ray Microtomography
PubMed: 31609958
DOI: 10.1097/SCS.0000000000005797 -
Ultrasound International Open Nov 2022Neurosonography evaluation of neonatal hypoxic-ischemic encephalopathy (HIE) is mainly qualitative. We aimed to quantitatively compare the echogenicity of several brain...
Neurosonography evaluation of neonatal hypoxic-ischemic encephalopathy (HIE) is mainly qualitative. We aimed to quantitatively compare the echogenicity of several brain regions in patients with HIE to healthy controls. 20 term neonates with clinical/MRI evidence of HIE and 20 term healthy neonates were evaluated. Seven brain regions were assessed [frontal, parietal, occipital, and perirolandic white matter (WM), caudate nucleus head, lentiform nucleus, and thalamus]. The echogenicity of the calvarial bones (bone) and the choroid plexus (CP) was used for ratio calculation. Differences in the ratios were determined between neonates with HIE and controls. Ratios were significantly higher for HIE neonates in each region (p<0.05). The differences were greatest for the perirolandic WM, with CP and bone ratios being 0.23 and 0.22 greater, respectively, for the HIE compared to the healthy neonates (p<0.001). The perirolandic WM had a high AUC, at 0.980 for both the CP and bone ratios. The intra-observer reliability for all ratios was high, with the caudate to bone ratio being the lowest at 0.832 and the anterior WM to CP ratio being the highest at 0.992. When coupled with internal controls, quantitative neurosonography represents a potential tool to identify early neonatal HIE changes. Larger cohort studies could reveal whether a quantitative approach can discern between degrees of severity of HIE. Future neurosonography protocols should be tailored to evaluate the perirolandic region, which requires posterior coronal scanning.
PubMed: 36408372
DOI: 10.1055/a-1958-3985 -
Molecules (Basel, Switzerland) Sep 2022Autologous bone is the gold standard in regeneration processes. However, there is an endless search for alternative materials in bone regeneration. Xenografts can act as... (Comparative Study)
Comparative Study
Autologous bone is the gold standard in regeneration processes. However, there is an endless search for alternative materials in bone regeneration. Xenografts can act as bone substitutes given the difficulty of obtaining bone tissue from patients and before the limitations in the availability of homologous tissue donors. Bone neoformation was studied in critical-size defects created in the parietal bone of 40 adult male Wistar rats, implanted with xenografts composed of particulate bovine hydroxyapatite (HA) and with blocks of bovine hydroxyapatite (HA) and Collagen, which introduces crystallinity to the materials. The Fourier-transform infrared spectroscopy (FTIR) analysis demonstrated the carbonate and phosphate groups of the hydroxyapatite and the amide groups of the collagen structure, while the thermal transitions for HA and HA/collagen composites established mainly dehydration endothermal processes, which increased (from 79 °C to 83 °C) for F2 due to the collagen presence. The xenograft's X-ray powder diffraction (XRD) analysis also revealed the bovine HA crystalline structure, with a prominent peak centered at 32°. We observed macroporosity and mesoporosity in the xenografts from the morphology studies with heterogeneous distribution. The two xenografts induced neoformation in defects of critical size. Histological, histochemical, and scanning electron microscopy (SEM) analyses were performed 30, 60, and 90 days after implantation. The empty defects showed signs of neoformation lower than 30% in the three periods, while the defects implanted with the material showed partial regeneration. InterOss Collagen material temporarily induced osteon formation during the healing process. The results presented here are promising for bone regeneration, demonstrating a beneficial impact in the biomedical field.
Topics: Amides; Animals; Bone Regeneration; Bone Substitutes; Cattle; Collagen; Durapatite; Heterografts; Humans; Male; Rats; Rats, Wistar
PubMed: 36144483
DOI: 10.3390/molecules27185745 -
Open Medicine (Warsaw, Poland) 2021In this study, a rare case with hemophilia pseudotumor in the skull was reported.
BACKGROUND
In this study, a rare case with hemophilia pseudotumor in the skull was reported.
CASE PRESENTATION
The case was a 34-year-old male patient who was admitted to the hospital, with the complaint of dizziness for more than 1 month. The physical examination indicated that the patient was conscious, who could give right answers to the questions. Moreover, there was a bulge on the left frontal-temporal parietal bone. The head CT showed abnormal density lesions on the left frontal-temporal parietal bone, with multiple irregular calcifications within the border. Skull MRI showed a large clump-like mixed signal at the top of the left frontal ridge. After admission, the patient was subjected to complete preoperative preparation and surgical treatment. Neurological navigation was used to determine the extent of skull defect before surgery to make a surgical incision. Clotting factor VIII substitution therapy was used for the intraoperative and postoperative treatments. The lesion was completely removed.
CONCLUSIONS
These results suggest that the skull hemophilia pseudotumor has been rarely seen. According to imaging examination, in combination with family history, the diagnosis can be confirmed. If there is no obvious occupying effect, conservative treatment can be tried. On the contrary, if there is an obvious occupying effect, surgical treatment might be effective, and coagulation factor VIII should be supplemented during the perioperative period.
PubMed: 33778161
DOI: 10.1515/med-2021-0245 -
Mechanisms of Development Dec 2019The zebrafish offers powerful advantages as a model system for examining the growth of the skull vault and the formation of cranial sutures. The zebrafish is well suited...
The zebrafish offers powerful advantages as a model system for examining the growth of the skull vault and the formation of cranial sutures. The zebrafish is well suited for large-scale genetic screens, available in large numbers, and continual advances in genetic engineering facilitate precise modeling of human genetic disorders. Most importantly, zebrafish are continuously accessible for imaging during critical periods of skull formation when both mouse and chick are physically inaccessible. To establish a foundation of information on the dynamics of skull formation, we performed a longitudinal study based on confocal microscopy of individual live transgenic zebrafish. Discrete events occur at stereotyped stages in overall growth, with little variation in timing among individuals. The frontal and parietal bones initiate as small clusters of cells closely associated with cartilage around the perimeter of the skull, prior to metamorphosis and the transition to juvenile fish. Over a period of ~30 days, the frontal and parietal bones grow towards the apex of the skull and meet to begin suture formation. To aid in visualization, we have generated interactive three-dimensional models based on the imaging data, with annotated cartilage and bone elements. We propose a framework to conceptualize development of bones of the skull vault in three phases: initiation in close association with cartilage; rapid planar growth towards the apex of the skull; and finally overlapping to form sutures. Our data provide an important framework for comparing the stages and timing of skull development across model organisms, and also a baseline for the examination of zebrafish mutants affecting skull development. To facilitate these comparative analyses, the raw imaging data and the models are available as an online atlas through the FaceBase consortium (facebase.org).
Topics: Animals; Animals, Genetically Modified; Imaging, Three-Dimensional; Morphogenesis; Osteogenesis; Skull; Zebrafish
PubMed: 31644945
DOI: 10.1016/j.mod.2019.103578 -
Zhongguo Yi Xue Ke Xue Yuan Xue Bao.... Apr 2022Objective To investigate the clinical and magnetic resonance imaging(MRI) manifestations of Rosai-Dorfman disease(RDD) in central nervous system. Method The clinical and...
Objective To investigate the clinical and magnetic resonance imaging(MRI) manifestations of Rosai-Dorfman disease(RDD) in central nervous system. Method The clinical and MRI data of 5 cases of RDD in central nervous system confirmed by pathology in the PLA General Hospital were analyzed retrospectively. Results The 5 cases included 4 males and 1 female,aged(39.8±21.7) years on average.Among them,4 cases were located in the intracranial area and 1 case in the thoracic spinal canal.The lesion showed isointense signal on T weighted image and iso,slight-hypo,and slight-hyperintense signals on T weighted image,and it presented intensively homogeneous enhancement in contrast-enhanced MRI.Two cases showed compressed brain area with edema around the left parietal and left frontotemporal dura,thickening and enhancement in the adjacent dura,and dural tail sign.Three cases presented bone destruction in adjacent diploe and thoracic vertebrae.One case showcased slight-hypo perfusion of the left parietal dura in arterial spin labeling. Conclusions RDD lesion usually appears as iso,slight hypo and slight hyper-intense signals on T weighted image and presents intensively homogeneous enhancement in contrast-enhanced MRI.The disease may involve the adjacent bone and the lesion shows slight hypo-perfusion on perfusion images.The MRI manifestations of RDD are characteristic,which are helpful for preoperative diagnosis and evaluation of RDD.
Topics: Central Nervous System; Female; Head; Histiocytosis, Sinus; Humans; Magnetic Resonance Imaging; Male; Retrospective Studies
PubMed: 35538751
DOI: 10.3881/j.issn.1000-503X.14703 -
The Journal of Pain Nov 2021Skeletal diseases and their surgical treatment induce severe pain. The innervation density of bone potentially explains the severe pain reported. Animal studies... (Observational Study)
Observational Study
Skeletal diseases and their surgical treatment induce severe pain. The innervation density of bone potentially explains the severe pain reported. Animal studies concluded that sensory myelinated A∂-fibers and unmyelinated C-fibers are mainly responsible for conducting bone pain, and that the innervation density of these nerve fibers was highest in periosteum. However, literature regarding sensory innervation of human bone is scarce. This observational study aimed to quantify sensory nerve fiber density in periosteum, cortical bone, and bone marrow of axial and appendicular human bones using immunohistochemistry and confocal microscopy. Multivariate Poisson regression analysis demonstrated that the total number of sensory and sympathetic nerve fibers was highest in periosteum, followed by bone marrow, and cortical bone for all bones studied. Bone from thoracic vertebral bodies contained most sensory nerve fibers, followed by the upper extremity, lower extremity, and parietal neurocranium. The number of nerve fibers declined with age and did not differ between male and female specimens. Sensory nerve fibers were organized as a branched network throughout the periosteum. The current results provide an explanation for the severe pain accompanying skeletal disease, fracture, or surgery. Further, the results could provide more insight into mechanisms that generate and maintain skeletal pain and might aid in developing new treatment strategies. PERSPECTIVE: This article presents the innervation of human bone and assesses the effect of age, gender, bone compartment and type of bone on innervation density. The presented data provide an explanation for the severity of bone pain arising from skeletal diseases and their surgical treatment.
Topics: Age Factors; Bone Diseases; Bone Marrow; Cortical Bone; Humans; Immunohistochemistry; Musculoskeletal Pain; Periosteum
PubMed: 33964414
DOI: 10.1016/j.jpain.2021.04.006 -
Gastroenterology Aug 2021The homeostasis of the gastrointestinal epithelium relies on cell regeneration and differentiation into distinct lineages organized inside glands and crypts....
BACKGROUND & AIMS
The homeostasis of the gastrointestinal epithelium relies on cell regeneration and differentiation into distinct lineages organized inside glands and crypts. Regeneration depends on Wnt/β-catenin pathway activation, but to understand homeostasis and its dysregulation in disease, we need to identify the signaling microenvironment governing cell differentiation. By using gastric glands as a model, we have identified the signals inducing differentiation of surface mucus-, zymogen-, and gastric acid-producing cells.
METHODS
We generated mucosoid cultures from the human stomach and exposed them to different growth factors to obtain cells with features of differentiated foveolar, chief, and parietal cells. We localized the source of the growth factors in the tissue of origin.
RESULTS
We show that epidermal growth factor is the major fate determinant distinguishing the surface and inner part of human gastric glands. In combination with bone morphogenetic factor/Noggin signals, epidermal growth factor controls the differentiation of foveolar cells vs parietal or chief cells. We also show that epidermal growth factor is likely to underlie alteration of the gastric mucosa in the precancerous condition atrophic gastritis.
CONCLUSIONS
Use of our recently established mucosoid cultures in combination with analysis of the tissue of origin provided a robust strategy to understand differentiation and patterning of human tissue and allowed us to draw a new, detailed map of the signaling microenvironment in the human gastric glands.
Topics: Body Patterning; Bone Morphogenetic Protein 4; Carrier Proteins; Cell Differentiation; Cell Lineage; Cells, Cultured; Cellular Microenvironment; Chief Cells, Gastric; Epidermal Growth Factor; Epithelial Cells; Gastric Mucosa; Gastritis, Atrophic; Gene Expression Regulation, Developmental; Humans; Organoids; Parietal Cells, Gastric; Wnt Signaling Pathway
PubMed: 33957136
DOI: 10.1053/j.gastro.2021.04.062 -
Surgical Neurology International 2022Angiomatous meningioma is a rare subtype of meningiomas. To the best of our knowledge, there have been no reports of intradiploic angiomatous meningioma.
BACKGROUND
Angiomatous meningioma is a rare subtype of meningiomas. To the best of our knowledge, there have been no reports of intradiploic angiomatous meningioma.
CASE DESCRIPTION
A 53-year-old previously healthy woman was diagnosed with a calvarial lesion during a brain checkup. Cerebral magnetic resonance imaging showed an intradiploic tumor, 11 × 14 × 12 mm, in the right parietal bone. It was an enhancing, lobular tumor presenting as isointensity on T1- and hyperintensity on T2-weighted sequences, with an intense enhancement of the adjacent dura mater. Computed tomography revealed bone erosion at the tumor site, extending predominantly into the inner side, and sclerotic changes in the surrounding bone. Total resection was performed. Microscopically, the tumor tissue comprised cells with low-grade meningioma and intervening prominent vasculatures, consistent with angiomatous meningioma.
CONCLUSION
Angiomatous meningioma should be considered as a differential diagnosis when an intradiploic tumor shows a lobular structure, intense enhancement of the adjacent dura mater, and sclerotic changes in the surrounding skull. These findings can support prompt tumor resection.
PubMed: 36128095
DOI: 10.25259/SNI_520_2022