Bone Endosteum Research Articles

Bmi-1 Epigenetically Orchestrates Osteogenic and Adipogenic Differentiation of Bone Marrow Mesenchymal Stem Cells to Delay Bone Aging.

With the increase in the aging population, senile osteoporosis (SOP) has become a major global public health concern. Here, it is found that Prx1 and Bmi-1 co-localized in trabecular bone, bone marrow cavity, endosteum, and periosteum. Prx1-driven Bmi-1 knockout in bone-marrow mesenchymal stem cells (BMSCs) reduced bone mass and increased bone marrow adiposity by inhibiting osteoblastic bone formation, promoting osteoclastic bone resorption, downregulating the proliferation and osteogenic differentiation of BMSCs, and upregulating the adipogenic differentiation of BMSCs. However, Prx1-driven Bmi-1 overexpression showed a contrasting phenotype to Prx1-driven Bmi-1 knockout in BMSCs. Regarding mechanism, Bmi-1-RING1B bound to DNMT3A and promoted its ubiquitination and inhibited DNA methylation of Runx2 at the region from 45047012 to 45047313bp, thus promoting the osteogenic differentiation of BMSCs. Moreover, Bmi-1-EZH2 repressed the transcription of Cebpa by promoting H3K27 trimethylation at the promoter region -1605 to -1596 bp, thus inhibiting the adipogenic differentiation of BMSCs. It is also found that Prx1-driven Bmi-1 overexpression rescued the SOP induced by Prx1-driven Bmi-1 knockout in BMSCs. Thus, Bmi-1 functioned as a hub protein in the epigenetic regulation of BMSCs differentiation to delay bone aging. The Prx1-driven Bmi-1 overexpression in BMSCs can be used as an approach for the translational therapy of SOP.

Study on the influence of cortical bone heterogeneity on the spatio-temporal distribution of drilling temperature

The degree of thermal damage during cortical bone drilling is an important factor in determining the success rate of surgery and postoperative recovery time. In this study, high and low feed rate drilling experiments are carried out on bovine femoral cortical bone by chisel edge thinning drill. Combined with the characterization of cortical bone tissue structure and the measurement results of important thermal property parameters, the potential impact mechanisms of cortical bone heterogeneity on the spatio-temporal distribution of drilling temperature and thermal damage are analyzed. The temperature rise rate and overheating duration at different distances from the hole wall in cortical bone drilling under different feed rates are also compared. The experimental results show that the specific heat gradually increases and the thermal conductivity gradually decreases from the periosteum to the endosteum. The hole wall temperature and thermal diffusion of cortical bone with different tissue structures are different under high and low feed rates. The closer to the cortical bone endosteum, the lower the drilling temperature, thermal diffusion and thermal damage area. This is not only related to the contact time between the drill bit and the hole wall of cortical bone with different tissue structures, but also closely related to the heterogeneous structure of cortical bone. In addition, it is found that in high feed rate cortical bone drilling, the temperature rise rate at different positions from the hole wall is higher and the overheating duration is shorter.

Characterization of adult human skeletal cells in different tissues reveals a CD90+CD34+ periosteal stem/progenitor population

The periosteum plays a crucial role in bone healing and is an important source of skeletal stem and progenitor cells. Recent studies in mice indicate that diverse populations of skeletal progenitors contribute to growth, homeostasis and healing. Information about the in vivo identity and diversity of skeletal stem and progenitor cells in different compartments of the adult human skeleton is limited. In this study, we compared non-hematopoietic populations in matched tissues from the femoral head and neck of 21 human participants using spectral flow cytometry of freshly isolated cells. High-dimensional clustering analysis indicated significant differences in marker distribution between periosteum, articular cartilage, endosteum and bone marrow populations, and identified populations that were highly enriched or unique to specific tissues. Periosteum-enriched markers included CD90 and CD34. Articular cartilage, which has very poor regenerative potential, showed enrichment of multiple markers, including the PDPN+CD73+CD164+CD146- population previously reported to represent human skeletal stem cells. We further characterized periosteal populations by combining CD90 with other strongly expressed markers. CD90+CD34+ cells sorted directly from periosteum showed significant colony-forming unit fibroblasts (CFU-F) enrichment, rapid expansion, and consistent multi-lineage differentiation of clonal populations in vitro. In situ, CD90+CD34+ cells include a perivascular population in the outer layer of the periosteum and non-perivascular cells closer to the bone surface. CD90+ cells are also highly enriched for CFU-F in bone marrow and endosteum, but not articular cartilage. In conclusion, our study indicates considerable diversity in the non-hematopoietic cell populations in different tissue compartments within the adult human skeleton, and suggests that periosteal progenitor cells reside within the CD90+CD34+ population.

New skeletal dose coefficients of the ICRP-110 reference phantoms for idealized external fields to photons and neutrons using dose response functions (DRFs)

The International Commission on Radiological Protection (ICRP) Publication 116 was released to provide a comprehensive dataset of the dose coefficients (DCs) for external exposures produced with the adult reference voxel phantoms of ICRP Publication 110. Although an advanced skeletal dosimetry method for photons and neutrons using fluence-to-dose response functions (DRFs) was introduced in ICRP Publication 116, the ICRP-116 skeletal DCs were calculated by using the simple method conventionally used (i.e., doses to red bone marrow and endosteum approximated by doses to spongiosa and/or medullary cavities). In the present study, the photon and neutron DRFs were used to produce skeletal DCs of the ICRP-110 reference phantoms, which were then compared with the ICRP-116 DCs. For photons, there were significant differences by up to ∼2.8 times especially at energies <0.3 MeV. For neutrons, the differences were generally small over the entire energy region (mostly <20%). The general impact of the DRF-based skeletal DCs on the effective dose calculations was negligibly small, supporting the validity of the ICRP-116 effective DCs despite their skeletal DCs derived from the simple method. Meanwhile, we believe that the DRF-based skeletal DCs could be beneficial in better estimates of skeletal doses of individuals for risk assessments.

Sympathetic Innervation Regulates Osteocyte-Mediated Cortical Bone Resorption during Lactation.

Bone undergoes constant remodeling by osteoclast bone resorption coupled with osteoblast bone formation at the bone surface. A third major cell type in the bone is osteocytes, which are embedded in the matrix, are well-connected to the lacunar network, and are believed to act as mechanical sensors. Here, it is reported that sympathetic innervation directly regulates lacunar osteocyte-mediated bone resorption inside cortical bone. It is found that sympathetic activity is elevated in different mouse models of bone loss, including lactation, ovariectomy, and glucocorticoid treatment. Further, during lactation elevated sympathetic outflow induces netrin-1 expression by osteocytes to further promote sympathetic nerve sprouting in the cortical bone endosteum in a feed-forward loop. Depletion of tyrosine hydroxylase-positive (TH+ ) sympathetic nerves ameliorated osteocyte-mediated perilacunar bone resorption in lactating mice. Moreover, norepinephrine activates β-adrenergic receptor 2 (Adrb2) signaling to promote secretion of extracellular vesicles (EVs) containing bone-degrading enzymes for perilacunar bone resorption and inhibit osteoblast differentiation. Importantly, osteocyte-specific deletion of Adrb2 or treatment with a β-blocker results in lower bone resorption in lactating mice. Together, these findings show that the sympathetic nervous system promotes osteocyte-driven bone loss during lactation, likely as an adaptive response to the increased energy and mineral demands of the nursing mother.

Incorporation of micro-CT-based detailed bone models into ICRP adult mesh-type reference computational phantoms

Objective. The red bone marrow (RBM) and bone endosteum (BE), which are required for effective dose calculation, are macroscopically modeled in the reference phantoms of the international commission on radiological protection (ICRP) due to their microscopic and complex histology. In the present study, the detailed bone models were developed to simplify the dose calculation process for skeletal dosimetry. Approach. The detailed bone models were developed based on the bone models developed at the University of Florida. A new method was used to update the definition of BE region by storing the BE location indices using virtual sub-voxels. The detailed bone models were then installed in the spongiosa regions of the ICRP mesh-type reference computational phantoms (MRCPs) via the parallel geometry feature of the Geant4 code. Main results. Comparing the results between the detailed-bone-installed MRCPs and the original MRCPs with the absorbed dose to spongiosa and fluence-to-dose response function (DRF)-based methods, the DRF-based method showed much smaller but still significant differences. Compared with the values given in ICRP Publications 116 and 133, the differences were very large (i.e. several orders of magnitudes), due mainly to the anatomical improvement of the skeletal system in the MRCPs; that is, spongiosa and medullary cavity are fully enclosed by cortical bone in the MRCPs but not in the ICRP-110 phantoms. Significance. The detailed bone models enable the direct calculation of the absorbed doses to the RBM and BE, simplifying the dose calculation process and potentially improving the consistency and accuracy of skeletal dosimetry.

Isolation and in vitro characterization of murine young-adult long bone skeletal progenitors.

Skeletal stem and progenitor cells (SSPCs) constitute a reservoir of bone-forming cells necessary for bone development, modeling and remodeling, as well as for fracture healing. Recent advances in tools to identify and isolate SSPCs have revealed that cells with multipotent properties are present not only in neonatal bone, but also in adult bone marrow and periosteum. The long bone metaphysis and endosteum have been proposed as an additional SSPC niche, although in vitro approaches to study their cellular and molecular characteristics are still limited. Here, we describe a comprehensive procedure to isolate and culture SSPCs derived from the metaphysis and endosteum of young-adult mice. Based on flow cytometry analysis of known SSPC markers, we found the presence of putative multipotent SSPCs, similar to neonatal bone tissue. In vitro, metaphyseal/endosteal SSPCs possess self-renewing capacity, and their multipotency is underscored by the ability to differentiate into the osteogenic and adipogenic lineage, while chondrogenic potential is limited. Expansion of metaphyseal/endosteal SSPCs under low oxygen conditions increases their proliferation capacity, while progenitor properties are maintained, likely reflecting their hypoxic niche in vivo. Collectively, we propose a validated isolation and culture protocol to study metaphyseal/endosteal SSPC biology in vitro.

Radiopharmacokinetic modelling and radiation dose assessment of 223Ra used for treatment of metastatic castration-resistant prostate cancer

PurposeRa-223 dichloride (223Ra, Xofigo®) is used for treatment of patients suffering from castration-resistant metastatic prostate cancer. The objective of this work was to apply the most recent biokinetic model for radium and its progeny to show their radiopharmacokinetic behaviour. Organ absorbed doses after intravenous injection of 223Ra were estimated and compared to clinical data and data of an earlier modelling study.MethodsThe most recent systemic biokinetic model of 223Ra and its progeny, developed by the International Commission on Radiological Protection (ICRP), as well as the ICRP human alimentary tract model were applied for the radiopharmacokinetic modelling of Xofigo® biodistribution in patients after bolus administration. Independent kinetics were assumed for the progeny of 223Ra. The time activity curves for 223Ra were modelled and the time integrated activity coefficients, overset{sim }{a}left({r}_S,{T}_Dright), in the source regions for each progeny were determined. For estimating the organ absorbed doses, the Specific Absorbed Fractions (SAF) and dosimetric framework of ICRP were used together with the aforementioned overset{sim }{a}left({r}_S,{T}_Dright) values.ResultsThe distribution of 223Ra after injection showed a rapid plasma clearance and a low urinary excretion. Main elimination was via faeces. Bone retention was found to be about 30% at 4 h post-injection. Similar tendencies were observed in clinical trials of other authors. The highest absorbed dose coefficients were found for bone endosteum, liver and red marrow, followed by kidneys and colon.ConclusionThe biokinetic modelling of 223Ra and its progeny may help to predict their distributions in patients after administration of Xofigo®. The organ dose coefficients of this work showed some variation to the values reported from clinical studies and an earlier compartmental modelling study. The dose to the bone endosteum was found to be lower by a factor of ca. 3 than previously estimated.

Development of skeletal systems for ICRP pediatric mesh-type reference computational phantoms

In 2016, the International Commission on Radiological Protection (ICRP) launched Task Group 103 (TG 103) for the explicit purpose of developing a new generation of adult and pediatric reference computational phantoms, named ‘mesh-type reference computational phantoms (MRCPs)’, that can overcome the limitations of voxel-type reference computational phantoms (VRCPs) of ICRP Publications 110 and 143 due to their finite voxel resolutions and the nature of voxel geometry. After completing the development of the adult MRCPs, TG 103 has started the development of pediatric MRCPs comprising 10 phantoms (male and female versions of the reference newborn, 1-year-old, 5-year-old, 10-year-old, and 15-year-old). As part of the TG 103 project, within the present study, the skeletal systems, one of the most important and complex organ systems of the body, were developed for each phantom age and sex. The developed skeletal systems, while closely preserving the original bone topology of the pediatric VRCPs, present substantial improvements in the anatomy of complex and/or small bones. In order to investigate the dosimetric impact of the developed skeletons, the average absorbed doses and the specific absorbed fractions for radiosensitive skeletal tissues (i.e. active marrow and bone endosteum) were computed for some selected external and internal exposure cases, which were then compared with those calculated with the skeletons of pediatric VRCPs. The comparison result showed that the dose values of the pediatric MRCPs were generally similar to those of the pediatric VRCPs for highly penetrating radiations (e.g. photons >200 keV); however, for weakly penetrating radiations (e.g. photons ⩽200 keV and electrons), significant differences up to a factor of 140 were observed.

Dosimetric considerations of 99mTc-MDP uptake within the epiphyseal plates of the long bones of pediatric patients

Skeletal scintigraphy is most performed in pediatric patients using the radiopharmaceutical 99mTc labelled methylene diphosphonate (99mTc-MDP). Reference biokinetic models for 99mTc-MDP indicate 50% of the administered activity is uniformly localized to the interior bone surfaces (trabecular and cortical regions), yet imaging data clearly show some preferential uptake to the epiphyseal growth plates of the long bones. To explore the dosimetric consequences of these regional activity concentrations, we have modified mesh-type computational phantoms of the International Commission on Radiological Protection (ICRP) reference pediatric series to explicitly include geometric models of the epiphyseal growth plates (2 mm in thickness) within the left/right, distal/proximal ends of the humeri, radii, ulnae, femora, tibia, and fibulae. Bone mineral activity from the ICRP Publication 128 biokinetic model for 99mTc-MDP (ICRP ) was then partitioned to the growth plates at values of 0.5%, 4.4%, 8.3%, 12.2%, 16.1%, and 20%. Radiation transport simulations were performed to compute 99mTc S-values and organ dose coefficients to the soft tissues and to bone site-specific regions of spongiosa. As the percentage of bone activity assigned to the growth plates was increased (from 0.5% to 20%), absorbed doses to the soft tissue organs, active bone marrow, bone endosteum (BE), as well as the detriment-weighted dose, were shown to decrease from their nominal values (no substantial growth plate activity), while epiphyseal plate self-doses increased. In the 15 year old male phantom, moving from 0.5% to 20% relative bone activity within the epiphyseal plates resulted in a 15% reduction in active marrow (AM) and BE dose, a 10% reduction in mean soft tissue and detriment-weighted dose, and a 6.3-fold increase in epiphyseal plate self-dose. In the newborn female phantom, we observed a 18% decrease in AM and BE dose, a 10% decrease in mean soft tissue dose, a 15% decrease in detriment-weighted dose, and 12.8-fold increase in epiphyseal plate self-dose. Increases (to 3 mm) and decreases (to 1 mm) in the assumed growth plate thickness of our models were shown to impact only the growth plate self-dose. Future work in differential quantification of 99mTc-MDP activity—growth plates versus other bone surfaces—is required to provide clinically realistic data on activity partitioning as a function of patient age, and perhaps skeletal site. The phantom series presented here may be used to develop more optimized age-related guidance on 99mTc-MDP administered activities to children.

A Scalable Database of Organ Doses for Common Diagnostic Fluoroscopy Procedures of Children: Procedures of Historical Practice for Use in Radiation Epidemiology Studies.

Assessment of health effects from low-dose radiation exposures in patients undergoing diagnostic imaging is an active area of research. High-quality dosimetry information pertaining to these medical exposures is generally not readily available to clinicians or epidemiologists studying radiation-related health risks. The purpose of this study was to provide methods for organ dose estimation in pediatric patients undergoing four common diagnostic fluoroscopy procedures: the upper gastrointestinal (UGI) series, the lower gastrointestinal (LGI) series, the voiding cystourethrogram (VCUG) and the modified barium swallow (MBS). Abstracted X-ray film data and physician interviews were combined to generate procedure outlines detailing X-ray beam projections, imaged anatomy, length of X-ray exposure, and presence and amount of contrast within imaged anatomy. Monte Carlo radiation transport simulations were completed for each of the four diagnostic fluoroscopy procedures across the 162-member (87 males and 75 females) University of Florida/National Cancer Institute pediatric phantom library, which covers variations in both subject height and weight. Absorbed doses to 28 organs, including the active marrow and bone endosteum, were assigned for all 162 phantoms by procedure. Additionally, we provide dose coefficients (DCs) in a series of supplementary tables. The DCs give organ doses normalized to procedure-specific dose metrics, including: air kerma-area product (µGy/mGy · cm2), air kerma at the reference point (µGy/µGy), number of spot films (SF) (µGy/number of SFs) and total fluoroscopy time (µGy/s). Organs accumulating the highest absorbed doses per procedure were as follows: kidneys between 0.9-25.4 mGy, 1.1-16.6 mGy and 1.1-9.7 mGy for the UGI, LGI and VCUG procedures, respectively, and salivary glands between 0.2-3.7 mGy for the MBS procedure. Average values of detriment-weighted dose, a phantom-specific surrogate for the effective dose based on ICRP Publication 103 tissue-weighting factors, were 0.98 mSv, 1.16 mSv, 0.83 mSv and 0.15 mSv for the UGI, LGI, VCUG and MBS procedures, respectively. Scalable database of organ dose coefficients by patient sex, height and weight, and by procedure exposure time, reference point air kerma, kerma-area product or number of spot films, allows clinicians and researchers to compute organ absorbed doses based on their institution-specific and patient-specific dose metrics. In addition to informing on patient dosimetry, this work has the potential to facilitate exposure assessments in epidemiological studies designed to investigate radiation-related risks.

Disruption of the preB Cell Receptor Complex Leads to Decreased Bone Mass.

In the bone marrow, preB cells are found adjacent to the bone endosteum where bone synthesizing osteoblast and bone resorbing osteoclasts reside. Although there is evidence of interactions between preB and bone cells, the factors that contribute to such interactions are poorly understood. A critical checkpoint for preB cell development assesses the integrity of the nascent immunoglobulin μ heavy chain (HC) by testing whether it can participate in the formation of a preB cell receptor (preBCR), composed of the μ HC and surrogate light chain (LC). In this work, we tested whether loss of preBCR components can affect bone synthesis. A panel of gene targeted mice with sequential blocks in preBCR formation or function [surrogate light chain component lambda 5 deleted (λ5−/−), transmembrane domain of μHC deleted (IgM-mem−/−), and CD19 preBCR co-receptor deleted (CD19−/−)] were evaluated for effects on postnatal bone synthesis. Postnatal bone mass was analyzed in 6 month old mice using μ-CT, histomorphometry and double calcein labeling. Both cortical and trabecular bone mass were significantly decreased in the femurs of the λ5 and IgM-mem deficient mice. Histomorphometric analysis showed a decrease in the numbers of osteoblasts and osteoclasts in all three mutant strains. Double calcein labeling revealed a significant decrease in dynamic synthesis and mineralization of bone in λ5−/− mice. Our data strongly suggest that interference with preBCR formation or function affects bone homeostasis independent of the presence or absence of mature B cells, and that components of the preBCR play important, and potentially distinct, roles in regulating adult bone mass.

An assessment of bone-seeking radionuclides for palliation of metastatic bone pain in a vertebral model.

Bone-seeking radiopharmaceuticals have the main role in the treatment of painful bone metastases. The aim of this study was to dosimetrically compare radiopharmaceuticals in use for bone pain palliation therapy and bone scan. The MCNPX code was used to simulate the radiation transport in a vertebral phantom. Absorbed fractions were calculated for monoenergetic electrons, photons and alpha particles. S values were obtained for radionuclides 32P, 33P, 89Sr, 90Y, 99mTc, 117mSn, 153Sm, 166Ho, 169Er, 177Lu, 186Re, 188Re, 223Ra, 224Ra and their progenies for target regions including the active marrow and the bone endosteum. The results demonstrated the dependence of dosimetric parameters on the source or target size, particle energy and location of the source. The electron emitters including 33P, 117mSn, 169Er and 177Lu and 223Ra as an α-emitter gave the lower absorbed dose to the active marrow. These radionuclides gave the highest values of the Relative Advantage Factor (RAF). According to the results,33P, 117mSn, 169Er, 177Lu and 223Ra have fewer side effects on the active marrow than other investigated radionuclides. Therefore, these radionuclides may be a better choice for use in palliative radiotherapy.

Abstract 1083A: An ex vivo 3D bone metastasis model for prostate cancer

Abstract Introduction: Bone is the preferred site for prostate cancer (PCa) metastases and there is virtually no cure once the tumor is established within this niche. The development of therapeutic strategies against metastatic PCa has been limited by the lack of an all-human preclinical model to: (1) study PCa-bone interactions under physiologically relevant three dimensional (3D) microenvironments, (2) understand how these interactions result in the development of drug resistance, and (3) explore paradigm-changing precision medicine concepts. Methods: Conditionally reprogrammed primary PCa cells (CR-PCa, derived from a lymph node metastatic site) were integrated with our ex vivo human 3D bone tissue platform, as a transformative approach for modeling tumor behavior at the bone niche. The 3D bone tissue was engineered using primary osteoblastic (OSB) cells from human bone samples. These cells were biomimetically assembly with biphasic calcium phosphate microbeads (BCPm) in perfusion microfluidic culture devices. BCPm were used to replicate the 3D cellular network of OSTs in human bone. This 3D tissue model was successfully used to support the osteocytic differentiation of primary human OSB cells within the BCPm structure, while maintaining a single cell layer of osteoblasts on the surface of the 3D tissue resembling the bone endosteum. Results: Integration of the 3D bone tissue with CR-PCa cells resulted in a compromised endosteal layer after only 4 days of coculture, with more apoptotic OSTs in the tissues with CR-PCa vs. no PCa cells controls (P&amp;lt;0.01). For functional analysis, we stained 5 μm sections of the 3D tissues for alkaline phosphatase (ALP, an OSB marker) and sclerostin, an osteocytic marker and major signaling molecule released by embedded OSTs that suppresses osteoblastogenesis. Quantification of immunofluorescence staining revealed that ALP was significantly increased (P&amp;lt;0.05), whereas sclerostin significantly decreased (P&amp;lt;0.01) with the introduction of CR-PCa cells. This OSB phenotype, induced by PCa-bone interactions ex vivo, is entirely consistent with the OSB prostate cancer-bone metastasis niche seen in patients with advanced disease. Conclusions: Our model recapitulates: (1) an OSB monolayer closely resembling the endosteum at the bone/ bone marrow interface, (2) the complex microphysiological features and functions of 3D-networked OSTs, and (3) the interactions of primary PCa cells with osteoblasts and OSTs. Citation Format: Jenny Zilberberg, Saba Choudhary, Eugenia Dziopa, Cirian Mannion, Yair Kissin, Erika Parasido, Christopher Albanese, Woo Lee. An ex vivo 3D bone metastasis model for prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1083A.

Targeted alpha-particle therapy: imaging, dosimetry, and radiation protection

Systemic or locoregionally administered alpha-particle emitters are highly potent therapeutic agents used in oncology that are fundamentally novel in their mechanism and, most likely, overcome radiation resistance as the alpha particles emitted have a short range and a high linear energy transfer. The use of alpha emitters in a clinic environment requires extra measures with respect to imaging, dosimetry, and radiation protection. This is shown for the example of 223Ra dichloride therapy. After intravenous injection, 223Ra leaves the blood and is taken up rapidly in bone and bone metastases; it is mainly excreted via the intestinal tract. 223Ra can be imaged in patients with a gamma camera. Dosimetry shows that, after a series of six treatments for a 70-kg person with an overall administered activity of 23 MBq, 223Ra results in an absorbed alpha dose of approximately 17 Gy to the bone endosteum and approximately 1.7 Gy to the red bone marrow. During administration, special care must be taken to ensure that no spill is present on the skin of either the patient or staff. Due to the low dose rate, the treatment is normally performed on an outpatient basis; the patient and carers should receive written instructions about the therapy and radiation protection.

Tenascin-C and Integrin α9 Mediate Interactions of Prostate Cancer with the Bone Microenvironment.

Deposition of the extracellular matrix protein tenascin-C is part of the reactive stroma response, which has a critical role in prostate cancer progression. Here, we report that tenascin C is expressed in the bone endosteum and is associated with formation of prostate bone metastases. Metastatic cells cultured on osteo-mimetic surfaces coated with tenascin C exhibited enhanced adhesion and colony formation as mediated by integrin α9β1. In addition, metastatic cells preferentially migrated and colonized tenascin-C-coated trabecular bone xenografts in a novel system that employed chorioallantoic membranes of fertilized chicken eggs as host. Overall, our studies deepen knowledge about reactive stroma responses in the bone endosteum that accompany prostate cancer metastasis to trabecular bone, with potential implications to therapeutically target this process in patients. Cancer Res; 77(21); 5977-88. ©2017 AACR.

The Promotional Effect of Mesenchymal Stem Cell Homing on Bone Tissue Regeneration.

In this paper, we review both systemic and local homing of MSCs during bone regeneration, and discuss strategies for enhancing the recruitment of MSCs to the injured bone tissues. Systemic influences of MSC homing are also discussed.

ELECTRON ABSORBED FRACTIONS IN AN IMAGE-BASED MICROSCOPIC SKELETAL DOSIMETRY MODEL OF CHINESE ADULT MALE.

Based on the Chinese reference adult male voxel model, a set of microscopic skeletal models of Chinese adult male is constructed through the processes of computed tomography (CT) imaging, bone coring, micro-CT imaging, image segmentation, merging into macroscopic bone model and implementation in Geant4. At the step of image segmentation, a new bone endosteum (BE) segmentation method is realized by sampling. The set of model contains 32 spongiosa samples with voxel size of 19 μm cubes. The microscopic spongiosa bone data for Chinese adult male are provided. Electron absorbed fractions in red bone marrow (RBM) and BE are calculated. Source tissues include the bone marrow (red and yellow), trabecular bone (surfaces and volumes) and cortical bone (surfaces and volumes). Target tissues include RBM and BE. Electron energies range from 10 keV to 10 MeV. Additionally, comparison of the result with other investigations is provided.

An image-based skeletal dosimetry model for the ICRP reference adult female—internal electron sources

An image-based skeletal dosimetry model for internal electron sources was created for the ICRP-defined reference adult female. Many previous skeletal dosimetry models, which are still employed in commonly used internal dosimetry software, do not properly account for electron escape from trabecular spongiosa, electron cross-fire from cortical bone, and the impact of marrow cellularity on active marrow self-irradiation. Furthermore, these existing models do not employ the current ICRP definition of a 50 µm bone endosteum (or shallow marrow). Each of these limitations was addressed in the present study. Electron transport was completed to determine specific absorbed fractions to both active and shallow marrow of the skeletal regions of the University of Florida reference adult female. The skeletal macrostructure and microstructure were modeled separately. The bone macrostructure was based on the whole-body hybrid computational phantom of the UF series of reference models, while the bone microstructure was derived from microCT images of skeletal region samples taken from a 45 years-old female cadaver. The active and shallow marrow are typically adopted as surrogate tissue regions for the hematopoietic stem cells and osteoprogenitor cells, respectively. Source tissues included active marrow, inactive marrow, trabecular bone volume, trabecular bone surfaces, cortical bone volume, and cortical bone surfaces. Marrow cellularity was varied from 10 to 100 percent for active marrow self-irradiation. All other sources were run at the defined ICRP Publication 70 cellularity for each bone site. A total of 33 discrete electron energies, ranging from 1 keV to 10 MeV, were either simulated or analytically modeled. The method of combining skeletal macrostructure and microstructure absorbed fractions assessed using MCNPX electron transport was found to yield results similar to those determined with the PIRT model applied to the UF adult male skeletal dosimetry model. Calculated skeletal averaged absorbed fractions for each source-target combination were found to follow similar trends of more recent dosimetry models (image-based models) but did not follow results from skeletal models based upon assumptions of an infinite expanse of trabecular spongiosa.

Development of skeletal system for mesh-type ICRP reference adult phantoms

The reference adult computational phantoms of the international commission on radiological protection (ICRP) described in Publication 110 are voxel-type computational phantoms based on whole-body computed tomography (CT) images of adult male and female patients. The voxel resolutions of these phantoms are in the order of a few millimeters and smaller tissues such as the eye lens, the skin, and the walls of some organs cannot be properly defined in the phantoms, resulting in limitations in dose coefficient calculations for weakly penetrating radiations. In order to address the limitations of the ICRP-110 phantoms, an ICRP Task Group has been recently formulated and the voxel phantoms are now being converted to a high-quality mesh format. As a part of the conversion project, in the present study, the skeleton models, one of the most important and complex organs of the body, were constructed. The constructed skeleton models were then tested by calculating red bone marrow (RBM) and endosteum dose coefficients (DCs) for broad parallel beams of photons and electrons and comparing the calculated values with those of the original ICRP-110 phantoms. The results show that for the photon exposures, there is a generally good agreement in the DCs between the mesh-type phantoms and the original voxel-type ICRP-110 phantoms; that is, the dose discrepancies were less than 7% in all cases except for the 0.03 MeV cases, for which the maximum difference was 14%. On the other hand, for the electron exposures (⩽4 MeV), the DCs of the mesh-type phantoms deviate from those of the ICRP-110 phantoms by up to ~1600 times at 0.03 MeV, which is indeed due to the improvement of the skeletal anatomy of the developed skeleton mesh models.