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Fibrous dysplasia (FD) is a rare benign skeletal disorder that replaces normal bone with fibrous tissue and immature woven bone. We present a case of a 13-year-old girl with right-sided facial swelling and craniofacial deformity since birth, accompanied by nasal obstruction and difficulty in breathing and swallowing. Computed tomography (CT) imaging revealed an expansile bony lesion with a ground-glass matrix involving multiple craniofacial bones. Histopathological examination confirmed the diagnosis of FD. Management involved regular monitoring and conservative measures, with surgical intervention reserved for symptomatic progression or cosmetic concerns. This case underscores the importance of considering FD in the differential diagnosis of craniofacial asymmetry and highlights the collaborative approach to patient care. Further research is needed to optimize management strategies and outcomes for pediatric patients with FD.
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Background: Disordered and hypomineralized woven bone formation by dysfunctional mesenchymal stromal cells (MSCs) characterize delayed fracture healing and endocrine -metabolic bone disorders like fibrous dysplasia and Paget disease of bone. To shed light on molecular players in osteoblast differentiation, woven bone formation, and mineralization by MSCs we looked at the intermediate filament desmin (DES) during the skeletogenic commitment of rat bone marrow MSCs (rBMSCs), where its bone-related action remains elusive. Results: Monolayer cultures of immunophenotypically- and morphologically - characterized, adult male rBMSCs showed co-localization of desmin (DES) with vimentin, F-actin, and runx2 in all cell morphotypes, each contributing to sparse and dense colonies. Proteomic analysis of these cells revealed a topologically-relevant interactome, focused on cytoskeletal and related enzymes//chaperone/signalling molecules linking DES to runx2 and alkaline phosphatase (ALP). Osteogenic differentiation led to mineralized woven bone nodules confined to dense colonies, significantly smaller and more circular with respect to controls. It significantly increased also colony-forming efficiency and the number of DES-immunoreactive dense colonies, and immunostaining of co-localized DES/runx-2 and DES/ALP. These data confirmed pre-osteoblastic and osteoblastic differentiation, woven bone formation, and mineralization, supporting DES as a player in the molecular pathway leading to the osteogenic fate of rBMSCs. Conclusion: Immunocytochemical and morphometric studies coupled with proteomic and bioinformatic analysis support the concept that DES may act as an upstream signal for the skeletogenic commitment of rBMSCs. Thus, we suggest that altered metabolism of osteoblasts, woven bone, and mineralization by dysfunctional BMSCs might early be revealed by changes in DES expression//levels. Non-union fractures and endocrine - metabolic bone disorders like fibrous dysplasia and Paget disease of bone might take advantage of this molecular evidence for their early diagnosis and follow-up.
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Adenocarcinoma , Doenças Ósseas Metabólicas , Calcinose , Células-Tronco Mesenquimais , Osteíte Deformante , Masculino , Animais , Ratos , Osteogênese , Filamentos Intermediários , Subunidade alfa 1 de Fator de Ligação ao Core , Desmina , Proteômica , Fosfatase AlcalinaRESUMO
We report on the 3D ultrastructure of the mineralized petrous bone of mature pig using focused ion beam - scanning electron microscopy (FIB-SEM). We divide the petrous bone into two zones based on the degree of mineralization; one zone close to the otic chamber has higher mineral density than the second zone further away from the otic chamber. The hypermineralization of the petrous bone results in the collagen D-banding being poorly revealed in the lower mineral density zone (LMD), and absent in the high mineral density zone (HMD). We therefore could not use D-banding to decipher the 3D structure of the collagen assembly. Instead we exploited the anisotropy option in the Dragonfly image processing software to visualize the less mineralized collagen fibrils and/or nanopores that surround the more mineralized zones known as tesselles. This approach therefore indirectly tracks the orientations of the collagen fibrils in the matrix itself. We show that the HMD bone has a structure similar to that of woven bone, and the LMD is composed of lamellar bone with a plywood-like structural motif. This agrees with the fact that the bone close to the otic chamber is fetal bone and is not remodeled. The lamellar structure of the bone further away from the otic chamber is consistent with modeling/remodeling. The absence of the less mineralized collagen fibrils and nanopores resulting from the confluence of the mineral tesselles may contribute to shielding DNA during diagenesis. We show that anisotropy evaluation of the less mineralized collagen fibrils could be a useful tool to analyze bone ultrastructures and in particular the directionality of collagen fibril bundles that make up the bone matrix.
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DNA Antigo , Odonatos , Animais , Suínos , Osso Petroso , Colágeno , MineraisRESUMO
During this presentation, a variety of class effects were reviewed by their differing effects on bone, including inhibition of endochondral ossification, inhibition of the growth hormone-insulin-like growth factor 1 axis, promotion of bone formation, inhibition of bone formation, abnormal bone formation, promotion of bone resorption, inhibition of bone resorption, and bone necrosis.
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Reabsorção Óssea , Osso e Ossos , Humanos , Osso e Ossos/metabolismo , OsteogêneseRESUMO
Existing in silico models for lamellar bone adaptation to mechanical loading are unsuitable for predicting woven bone growth. This anomaly is due to the difference in mechanobiology of the woven bone with respect to that of the lamellar bone. The present study is aimed at developing an in silico bone-adaptation model for woven bone at cellular and tissue levels. The diffusion of Ca2+ ions reaching lining cells from the osteocytic network and the bone cortex in response to a mechanical loading on the cortical bone has been considered as a stimulus. The diffusion of ions within osteocytic network has been computed with a lacunar-canalicular network (LCN) in which bone cells are uniformly arranged. Strain energy density is assumed to regulate ion flow within the network when the induced normal strain is above a threshold level. If the induced strain exceeds another higher threshold level, then the strain with a power constant is additionally assumed to regulate the stimulus. The intracellular flow of Ca2+ ions within the LCN has been simulated using Fick's laws of diffusion, using a finite element method. The ion diffusion from bone cortex to vesicles has been formulated as a normal strain with a power constant. The stimuli reaching the surface cells are assumed to form the new bone. The mathematical model closely predicts woven bone growth in mouse and rat tibia for various in vivo loading conditions. This model is the first to predict woven bone growth at tissue and cellular levels in response to heavy mechanical loading.
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Osteócitos , Tíbia , Camundongos , Ratos , Animais , Tíbia/fisiologia , Desenvolvimento Ósseo/fisiologia , Simulação por Computador , Osso e OssosRESUMO
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) cell area/total area X 100 indicating the percentage of an area occupied by cells (cellularity index) and ii) total area/number of cells (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 total area/number of cells 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.
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The woven bone created during the healing of bone regeneration processes is characterized as being extremely inhomogeneous and having a variable stiffness that increases with time. Therefore, it is important to study how the mechanical properties of woven bone are dependent on its microarchitecture and especially on its porosity and mineral content. The porosity and the x-ray greyscale of specimens taken from bone transport studies in sheep were assessed by means of ex vivo imaging. Our study demonstrates that the porosity of the woven bone in the distraction area diminishes during the healing process from 73.3% 35 days after surgery to 31.9% 525 days after surgery. In addition, the woven bone's porosity is negatively correlated with its Young's modulus. The x-ray greyscale, was measured as an indicator of the level of mineralization of the woven bone. Greyscale index has been demonstrated to be inversely proportional to porosity and to increase to up to 60-80% of the level in cortical bone. The results of this study may contribute to the development of micromechanical models of woven bone and improvements in in silico modelling.
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Osso e Ossos/fisiologia , Animais , Osso e Ossos/diagnóstico por imagem , Módulo de Elasticidade , Membro Posterior , Porosidade , Ovinos , Raios XRESUMO
Juvenile Paget's disease (JPD) became in 1974 the commonly used name for ultra-rare heritable occurrences of rapid bone remodeling throughout of the skeleton that present in infancy or early childhood as fractures and deformity hallmarked biochemically by marked elevation of serum alkaline phosphatase (ALP) activity (hyperphosphatasemia). Untreated, JPD can kill during childhood or young adult life. In 2002, we reported that homozygous deletion of the gene called tumor necrosis factor receptor superfamily, member 11B (TNFRSF11B) encoding osteoprotegerin (OPG) explained JPD in Navajos. Soon after, other bi-allelic loss-of-function TNFRSF11B defects were identified in JPD worldwide. OPG inhibits osteoclastogenesis and osteoclast activity by decoying receptor activator of nuclear factor κ-B (RANK) ligand (RANKL) away from its receptor RANK. Then, in 2014, we reported JPD in a Bolivian girl caused by a heterozygous activating duplication within TNFRSF11A encoding RANK. Herein, we identify mutation of a third gene underlying JPD. An infant girl began atraumatic fracturing of her lower extremity long-bones. Skull deformity and mild hearing loss followed. Our single investigation of the patient, when she was 15â¯years-of-age, showed generalized osteosclerosis and hyperostosis. DXA revealed a Z-score of +5.1 at her lumbar spine and T-score of +3.3 at her non-dominant wrist. Biochemical studies were consistent with positive mineral balance and several markers of bone turnover were elevated and included striking hyperphosphatasemia. Iliac crest histopathology was consistent with rapid skeletal remodeling. Measles virus transcripts, common in classic Paget's disease of bone, were not detected in circulating mononuclear cells. Then, reportedly, she responded to several months of alendronate therapy with less skeletal pain and correction of hyperphosphatasemia but had been lost to our follow-up. After we detected no defect in TNFRSF11A or B, trio exome sequencing revealed a de novo heterozygous missense mutation (c.926C>G; p.S309W) within SP7 encoding the osteoblast transcription factor osterix (specificity protein 7, transcription factor SP7). Thus, mutation of SP7 represents a third genetic cause of JPD.
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Osteíte Deformante , Pré-Escolar , Feminino , Homozigoto , Humanos , Mutação/genética , Osteíte Deformante/genética , Osteoprotegerina/genética , Ligante RANK , Deleção de Sequência , Fator de Transcrição Sp7 , Fatores de Transcrição , Adulto JovemRESUMO
Grafting bone substitute is paramount to prevent the alveolar ridge resorption after tooth extraction and facilitate the subsequent implant treatment. An ideal bone substitute should acquire the excellent osteogenic property, more importantly, possess the suitable remodeling rate in balance with bone formation and desirable clinical manageability. However, none of bone substitute is simultaneously characterized by these features, and currently, the limited remodeling property leads to the excessive waiting time before implantation. Enlightened by woven bone, the transitional tissue that is able to induce osteogenesis during bone healing could be easily remodeled within a short period and depend on the favorable injectability of hydrogel, an injectable woven bone-like hydrogel (IWBLH) was constructed in this study to address the above problems. To mimic the component and hierarchical structure of woven bone, amorphous calcium phosphate (ACP) and mineralized collagen fibril were synthesized and compounded with alginate to form IWBLHs with various ratio. Screened by physiochemical characterization and in vitro biological assays, an optimal IWBLH was selected and further explored in rat model of tooth extraction. Compared with the most widely used bone substitute, we showed that IWBLH could be easily handled to fully fill the tooth socket, perform a comparable function to prevent the alveolar bone resorption, and completely remodeled within 4 weeks. This IWBLH stands as a promising candidate for alveolar ridge preservation (ARP) in future.
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OBJECTIVES: Denosumab is Receptor Activator of Nuclear factor Kappa-B Ligand (RANKL) inhibitor which is being used in the treatment of locally advanced, recurrent and metastatic Giant Cell Tumor of Bone (GCTB). It causes reduction in monocyte recruitment and Osteoclast-Like Giant Cell (OLGC) formation which limits bone destruction. After Denosumab treatment, GCTB exhibit diverse morphological features which can pose diagnostic challenge. Our aim was to study the spectrum of histologic features seen in Denosumab treated GCTB which could be helpful in establishing correct diagnosis. METHODS: We retrieved and reviewed H&E stained microscopic glass slides of 38 GCTB cases who received Denosumab as neoadjuvant treatment. These cases were treated at different institutes and diagnosed at our institute between January 2017 and October 2019. Morphologic features such as presence of residual OLGC, appearances of mononuclear stromal and bony components were assessed along with other non-specific features. RESULTS: Patients' median age was 29 years. Male to female ratio was 1.53:1. Femur was the most commonly involved bone. Microscopically, peripheral shell of reactive bone was observed in all cases. In 20 (52.6%) cases, there was complete elimination of OLGC. Mononuclear stromal cells were predominantly bland spindle shaped and arranged in fascicular and storiform patterns. Focal atypia was noted in 3 cases. Bony component manifested as trabeculae of woven bone with osteoblastic rimming and immature trabeculae of unmineralized osteoid with haphazardly present osteoblasts. Spectrum of stromal changes included cystic spaces, foamy macrophages, inflammatory infiltrate, hemangiopericytoma-like (HPC-like) vessels, hyalinization, edematous areas and hemosiderin pigment. The tumors showed areas which resembled other bony and soft tissue lesions such non-ossifying fibroma, fibrous dysplasia, osteoblastoma, sclerosing epithelioid fibrosarcoma and osteosarcoma. CONCLUSION: Denosumab treatment induces a variety of changes in GCTB. Clinical history and knowledge of these features are necessary for excluding differential diagnoses and avoiding misdiagnosis.
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Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/patologia , Denosumab/uso terapêutico , Tumor de Células Gigantes do Osso/diagnóstico , Tumor de Células Gigantes do Osso/tratamento farmacológico , Adulto , Estudos Transversais , Diagnóstico Diferencial , Erros de Diagnóstico/prevenção & controle , Feminino , Fêmur/patologia , Tumor de Células Gigantes do Osso/cirurgia , Tumor de Células Gigantes do Osso/ultraestrutura , Humanos , Masculino , Osteoclastos/efeitos dos fármacos , Osteoclastos/patologia , Patologistas , Ligante RANK/antagonistas & inibidores , Células Estromais/efeitos dos fármacos , Células Estromais/patologiaRESUMO
This study explores the application of synchrotron radiation and conventional microcomputed tomography (SR-µCT and C-µCT, respectively) in evaluating bone-biopsy specimens. Bone-biopsy specimens were obtained using a trephine bur during bone-graft removal for implant placement six months after performing a maxillary sinus bone-graft procedure. Image data of specimens were obtained using SR-µCT and C-µCT. SR-µCT was performed using the 6C biomedical imaging beamline at the Pohang Accelerator Laboratory with a monochromatic X-ray beam of 23â keV, and C-µCT was performed using a table-top CT scanner (Skyscan 1272). Reconstruction images obtained using the two methods were qualitatively compared with 2D images evaluated under 3D visualization. The SR-µCT images, especially of the new-bone-graft-woven-bone formation, were less noisy and sharper than the C-µCT images. To evaluate the new-bone-graft-woven-bone formation, only the SR-µCT images showed areas of new bone (NB) formation with bone substitute (BS; Bio-Oss) and woven bone (WB) contact, and correctly visualized true 3D structures of bone formation. Hence, µCT techniques are non-destructive and can provide detailed images of bone biopsy. In particular, SR-µCT can be used to obtain improved image quality with contrast of NB, BS and WB, demonstrating a level of detail comparable with bone formation. SR-µCT could be an unbiased 3D alternative for imaging WB formation and for high-throughput analysis.
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Regeneração Óssea , Osso e Ossos/ultraestrutura , Síncrotrons , Microtomografia por Raio-X/métodos , Absorção de Radiação , Biópsia , Humanos , Processamento de Imagem Assistida por Computador , Imageamento Tridimensional , Maxila/patologia , Maxila/cirurgia , RefratometriaRESUMO
INTRODUCTION: Physiological stress is one of the various factors that can have an impact on stable isotope ratios. However, its effect on bone collagen stable isotope ratios is still not fully understood. This study aims to build on previous research on how different disease stages may affect bone collagen stable isotope ratios. MATERIALS AND METHODS: Carbon (δ13 C) and nitrogen (δ15 N) isotope ratios were assessed in 33 skeletons that retained evidence of infectious disease and healed fractures. Samples were taken from active lesions (long bones n = 14; ribs n = 4), healed lesions (long bones n = 10; ribs n = 9), or a fracture callus (long bones n = 9; ribs n = 3). Results were compared to stable isotope ratios calculated for regions on these bones that did not retain evidence of disease or fracture. RESULTS: Long bones with active lesions had a significantly higher average δ15 N (δ15 N = 11.1 ± 0.9) compared to those without lesions (δ15 N = 10.7 ± 0.7; p = .02), while fracture calluses showed the largest range for both δ15 N and δ13 C. There were no significant differences in stable isotope ratios when compared between nonlesion and lesion sites in the ribs. DISCUSSION: The increase in δ15 N seen in active lesions, when compared with δ15 N from nonlesion regions on the same long bone, may be a consequence of altered protein metabolism. The high variability of δ15 N and δ13 C in fractures may be related to different healing stages of the calluses. This study suggests that stable isotope data can contribute information about diseases in the past, as well as an individual's response to diseases in the absence of modern medicine and antibiotics.
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Osso e Ossos/química , Consolidação da Fratura , Adulto , Idoso , Doenças Ósseas/fisiopatologia , Isótopos de Carbono/análise , Feminino , Fraturas Ósseas/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Isótopos de Nitrogênio/análise , Portugal , Adulto JovemRESUMO
The proportion of woven bone (WB) to parallel-fibered bone has been extensively used to infer bone growth rates and resting metabolic rates of extinct organisms. The aim of this study is to test in a variety of amniotes how reliably WB content can be measured using transverse sections. For this, we analyzed femoral transverse mid-diaphyseal thin sections of 14 extant and extinct taxa and the corresponding longitudinal sections for comparative purposes. We used the following characters to identify WB in transverse sections because they are known to be distinct from those observed in parallel-fibered bone: an isotropic bone matrix at tissue scale; an anisotropic microlamellar arrangement in former osteoblast secretory territories at cellular scale; no alignment between osteocytes; and canaliculi running radially from large irregular osteocyte lacunae. Our null hypothesis predicts no differences between the amount of WB quantified in the transverse and longitudinal sections of a given long bone. Qualitatively, when a stripe or a patch of WB was identified in a transverse section, the corresponding stripe or patch of WB was always found at the same location in the corresponding longitudinal section. Quantitatively, a Wilcoxon signed-rank nonparametric paired test did not detect a significant difference in the WB content of the two section planes. Thus, the null hypothesis is not rejected. Considering that paleohistology is a destructive method, we recommend a workflow to efficiently establishing the proportion of WB: quantifying it in transverse sections; preparing and analyzing longitudinal sections only in cases where an ambiguity remains; reanalyzing the corresponding transverse sections.
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Osso e Ossos/anatomia & histologia , Osso e Ossos/fisiologia , Paleontologia , Vertebrados/anatomia & histologia , Animais , Anisotropia , Fêmur/anatomia & histologia , Osteócitos/citologiaRESUMO
Woven tissue is mainly present in the bone callus, formed very rapidly either after a fracture or in distraction processes. This high formation speed is probably responsible for its disorganized microstructure and this, in turn, for its low stiffness. Nonetheless, the singular volumetric composition of this tissue may also play a key role in its mechanical properties. The volumetric composition of woven tissue extracted from the bone transport callus of sheep was investigated and compared with that of the lamellar tissue extracted from the cortical shell of the same bone. Significant differences were found in the mineral and water contents, but they can be due to the different ages of both tissues, which affects the mineral/water ratio. However, the content in organic phase remains more or less constant throughout the mineralization process and has proven to be a good variable to measure the different composition of both tissues, being that content significantly higher in woven tissue. This may be linked to the abnormally high concentration of osteocytes in this tissue, which is likely a consequence of the more abundant presence of osteoblasts secreting osteoid and burying other osteoblasts, which then differentiate into osteocytes. This would explain the high formation rate of woven tissue, useful to recover the short-term stability of the bone. Nonetheless, the more abundant presence of organic phase prevents the woven tissue from reaching a stiffness similar to that of lamellar tissue in the long term, when it is fully mineralized.
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Calo Ósseo/patologia , Animais , Feminino , Tamanho do Órgão , OvinosRESUMO
Most osteolytic tumors are in fact mixed and contain an osteoblastic component associated with the predominant osteolytic areas. This metaplastic woven bone is always evidenced by histological analysis even in the absence of radiological expression. Metaplastic bone formation reflects the activation of new osteoblasts coming from the stimulation of the dormant lining cells. Twelve patients with secondary metastases of the iliac crest evidenced by hot spots on a 99Tc-MBP san were diagnosed by histomorphometry on bone biopsies. Fourier Transformed InfraRed analysis and Imaging (FTIRI) was used on 4µm thick sections of undecalcified bone. The mineralization degree, carbonate substitution, crystallinity and the cross-links ratio of collagen (1660/1690cm-1 bands) were determined. The matrix characteristics were analyzed and imaged in the pre-existing residual bone and in the metaplastic woven bone in the vicinity of the tumor cells. FTIRI provided images of the phosphate, amide and combination of peak ratio after having selected the peaks of interest. In addition, the matrix properties can be measured and compared between the old and newly-formed bones. Woven bone appeared poorly calcified with a low phosphate/amide ratio (P=0.03) crystallinity (P<0.0001) and carbonate substitution (P=0.003). Collagen was less mature as evidenced by lower cross-links (P=0.01). Woven bone associated with bone metastasis appears poorly mineralized and rapidly elaborated by osteoblasts. The collagenous phase of the bone matrix has a low level of reticulation. FTIRI is a powerful tool to measure and visualize the various components of the bone matrix in human diseases.
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Densidade Óssea , Neoplasias Ósseas/diagnóstico por imagem , Ílio/diagnóstico por imagem , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Biópsia , Matriz Óssea/diagnóstico por imagem , Matriz Óssea/patologia , Neoplasias Ósseas/patologia , Neoplasias Ósseas/secundário , Estudos de Viabilidade , Feminino , Humanos , Ílio/patologia , Masculino , Osteogênese , Estudos Retrospectivos , Medronato de Tecnécio Tc 99m/administração & dosagemRESUMO
Acral angioosteoma cutis is a rare and benign cutaneous lesion clinically characterized by an exophytic growth resembling pyogenic granuloma on the acral skin; first described in 2006. Its pathogenesis is still unclear while well-formed capillaries, pale stroma, bland fibroblast-like cells, and multiple tiny spicules of woven bone constitute the histological hallmarks. Here, we present a case of acral angioosteoma cutis in a 34-year-old man to increase awareness regarding this rare condition.
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Eritema/diagnóstico , Eritema/cirurgia , Polegar/patologia , Polegar/cirurgia , Adulto , Humanos , Masculino , Dermatopatias/diagnóstico , Dermatopatias/cirurgiaRESUMO
Nanoindentation has been used successfully in the determination of the mechanical properties of bone. Its application in fracture healing provides information on the evolution of material properties of the woven bone during regeneration process. However, this technique has not been applied in assessing the mechanical properties of woven bone during distraction osteogenesis. Therefore, the aim of this work is to evaluate the spatial and temporal variations of the elastic modulus of the woven bone generated during the bone transport process. Callus samples were harvested from intervened animals at different time points during the bone transport process (35, 50, 79, 98, 161 and 525 days after surgery) for nanoindentation measurements. Results clearly showed that the mean elastic modulus of the woven bone increased during the bone transport process reaching 77% of value for cortical bone after 525 days (from 7GPa 35 days after surgery to 14GPa 525 days after surgery approximately). Woven bone generated during bone transport seems to present similar evolution of elastic modulus with time as values reported for fracture healing. Furthermore, different spatial variations of elastic modulus within the callus were found for different stages of the process.
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Regeneração Óssea , Calo Ósseo/fisiologia , Consolidação da Fratura , Osteogênese por Distração , Animais , Módulo de Elasticidade , Ovinos , Análise Espaço-TemporalRESUMO
Human dental pulp stem cells (hDPSCs) are mesenchymal stem cells that have been successfully used in human bone tissue engineering. To establish whether these cells can lead to a bone tissue ready to be grafted, we checked DPSCs for their osteogenic and angiogenic differentiation capabilities with the specific aim of obtaining a new tool for bone transplantation. Therefore, hDPSCs were specifically selected from the stromal-vascular dental pulp fraction, using appropriate markers, and cultured. Growth curves, expression of bone-related markers, calcification and angiogenesis as well as an in vivo transplantation assay were performed. We found that hDPSCs proliferate, differentiate into osteoblasts and express high levels of angiogenic genes, such as vascular endothelial growth factor and platelet-derived growth factor A. Human DPSCs, after 40 days of culture, give rise to a 3D structure resembling a woven fibrous bone. These woven bone (WB) samples were analysed using classic histology and synchrotron-based, X-ray phase-contrast microtomography and holotomography. WB showed histological and attractive physical qualities of bone with few areas of mineralization and neovessels. Such WB, when transplanted into rats, was remodelled into vascularized bone tissue. Taken together, our data lead to the assumption that WB samples, fabricated by DPSCs, constitute a noteworthy tool and do not need the use of scaffolds, and therefore they are ready for customized regeneration.
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Substitutos Ósseos , Polpa Dentária/citologia , Células-Tronco/citologia , Engenharia Tecidual/métodos , Adulto , Animais , Transplante Ósseo/métodos , Calcificação Fisiológica/fisiologia , Diferenciação Celular/fisiologia , Proliferação de Células , Separação Celular/métodos , Células Cultivadas , Quimiotaxia , Humanos , Camundongos Nus , Neovascularização Fisiológica/fisiologia , Osteocalcina/metabolismo , Osteogênese/fisiologia , Microtomografia por Raio-X/métodos , Adulto JovemRESUMO
Woven bone is a type of tissue that forms mainly during fracture healing or fetal bone development. Its microstructure can be modeled as a composite with a matrix of mineral (hydroxyapatite) and inclusions of collagen fibrils with a more or less random orientation. In the present study, its elastic properties were estimated as a function of composition (degree of mineralization) and fibril orientation. A self-consistent homogenization scheme considering randomness of inclusions' orientation was used for this purpose. Lacuno-canalicular porosity in the form of periodically distributed void inclusions was also considered. Assuming collagen fibrils to be uniformly oriented in all directions led to an isotropic tissue with a Young's modulus [Formula: see text] GPa, which is of the same order of magnitude as that of woven bone in fracture calluses. By contrast, assuming fibrils to have a preferential orientation resulted in a Young's modulus in the preferential direction of 9-16 GPa depending on the mineral content of the tissue. These results are consistent with experimental evidence for woven bone in foetuses, where collagen fibrils are aligned to a certain extent.
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Osso e Ossos/química , Osso e Ossos/citologia , Colágeno/metabolismo , Durapatita/metabolismo , Módulo de Elasticidade , Feto/fisiologia , Humanos , PorosidadeRESUMO
Skeletal metastases present a major clinical challenge for prostate cancer patient care, inflicting distinctive mixed osteoblastic and osteolytic lesions that cause morbidity and refractory skeletal complications. Macrophages are abundant in bone and bone marrow and can influence both osteoblast and osteoclast function in physiology and pathology. Herein, we examined the role of macrophages in prostate cancer bone lesions, particularly the osteoblastic response. First, macrophage and lymphocyte distributions were qualitatively assessed in patient's prostate cancer skeletal lesions by immunohistochemistry. Second, macrophage functional contributions to prostate tumour growth in bone were explored using an immune-competent mouse model combined with two independent approaches to achieve in vivo macrophage depletion: liposome encapsulated clodronate that depletes phagocytic cells (including macrophages and osteoclasts); and targeted depletion of CD169(+) macrophages using a suicide gene knock-in model. Immunohistochemistry and histomorphometric analysis were performed to quantitatively assess cancer-induced bone changes. In human bone metastasis specimens, CD68(+) macrophages were consistently located within the tumour mass. Osteal macrophages (osteomacs) were associated with pathological woven bone within the metastatic lesions. In contrast, lymphocytes were inconsistently present in prostate cancer skeletal lesions and when detected, had varied distributions. In the immune-competent mouse model, CD169(+) macrophage ablation significantly inhibited prostate cancer-induced woven bone formation, suggesting that CD169(+) macrophages within pathological woven bone are integral to tumour-induced bone formation. In contrast, pan-phagocytic cell, but not targeted CD169(+) macrophage depletion resulted in increased tumour mass, indicating that CD169(-) macrophage subset(s) and/or osteoclasts influenced tumour growth. In summary, these observations indicate a prominent role for macrophages in prostate cancer bone metastasis that may be therapeutically targetable to reduce the negative skeletal impacts of this malignancy, including tumour-induced bone modelling. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.