Studies on the Relationship between Bone Strength and Bone Quality in Rats Fed with a Low-magnesium Diet

AbstractThe relationship between bone strength and bone quality in rats fed with a low-magnesium (low-Mg) diet was examined. Twenty four-week-old male Wistar rats were divided into a control group (n = 10) and a low-Mg group (n = 10). Each group was fed with a conventional diet or a low-Mg diet (Mg, 6 mg/100 g diet) for 8 weeks, respectively. After the rats were sacrificed, bone strength, bone mineral content (BMC) and three-dimensional (3D) trabecular structure of the lumbar vertebra were measured, respectively. The results showed that the values of the BMC were almost the same between the control and the low-Mg diet groups. On the other hand, the bone strength of the low-Mg diet group was significantly lower than that of the control group (p < 0.01). 3D trabecular structure analysis showed a significant decrease (p < 0.05 or 0.01) in the trabecular structure of the low-Mg diet group as compared to the control group. These findings suggest that the bone strength in this model is not affected by the BMC but is strongly affected by the trabecular structure. The low-Mg diet model is considered to be an excellent model for examining bone quality

New Particle Identification Approach with Convolutional Neural Networks in GAPS

The General Antiparticle Spectrometer (GAPS) is a balloon-borne experiment that aims to measure low-energy cosmic-ray antiparticles. GAPS has developed a new antiparticle identification technique based on exotic atom formation caused by incident particles, which is achieved by ten layers of Si(Li) detector tracker in GAPS. The conventional analysis uses the physical quantities of the reconstructed incident and secondary particles. In parallel with this, we have developed a complementary approach based on deep neural networks. This paper presents a new convolutional neural network (CNN) technique. A three-dimensional CNN takes energy depositions as three-dimensional inputs and learns to identify their positional/energy correlations. The combination of the physical quantities and the CNN technique is also investigated. The findings show that the new technique outperforms existing machine learning-based methods in particle identification.Comment: 7 pages, 10 figure

The matrix vesicle cargo miR-125b accumulates in the bone matrix, inhibiting bone resorption in mice

Communication between osteoblasts and osteoclasts plays a key role in bone metabolism. We describe here an unexpected role for matrix vesicles (MVs), which bud from boneforming osteoblasts and have a well-established role in initiation of bone mineralization, in osteoclastogenesis. We show that the MV cargo miR-125b accumulates in the bone matrix, with increased accumulation in transgenic (Tg) mice overexpressing miR-125b in osteoblasts. Bone formation and osteoblasts in Tg mice are normal, but the number of bone-resorbing osteoclasts is reduced, leading to higher trabecular bone mass. miR-125b in the bone matrix targets and degrades Prdm1, a transcriptional repressor of anti-osteoclastogenic factors, in osteoclast precursors. Overexpressing miR-125b in osteoblasts abrogates bone loss in different mouse models. Our results show that the MV cargo miR-125b is a regulatory element of osteoblast-osteoclast communication, and that bone matrix provides extracellular storage of miR-125b that is functionally active in bone resorption.T.M. and Y.T. were supported in part by MEXT KAKENHI (JP16K11443, T.M.; JP26861548, Y.T.). Y.Y. was supported by MEXT KAKENHI (JP18K19647), the Raffinee International Foundation and the Ono Pharmaceutical Foundation.Supplementary information is available for this paper at https://doi.org/10.1038/s42003-020-0754-2

A novel underuse model shows that inactivity but not ovariectomy determines the deteriorated material properties and geometry of cortical bone in the tibia of adult rats

Our goal in this study was to determine to what extent the physiologic consequences of ovariectomy (OVX) in bones are exacerbated by a lack of daily activity such as walking. We forced 14-week-old female rats to be inactive for 15 weeks with a unique experimental system that prevents standing and walking while allowing other movements. Tibiae, femora, and 4th lumbar vertebrae were analyzed by peripheral quantitative computed tomography (pQCT), microfocused X-ray computed tomography (micro-CT), histology, histomorphometry, Raman spectroscopy, and the three-point bending test. Contrary to our expectation, the exacerbation was very much limited to the cancellous bone parameters. Parameters of femur and tibia cortical bone were affected by the forced inactivity but not by OVX: (1) cross-sectional moment of inertia was significantly smaller in Sham-Inactive rat bones than that of their walking counterparts; (2) the number of sclerostin-positive osteocytes per unit cross-sectional area was larger in Sham-Inactive rat bones than in Sham-Walking rat bones; and (3) material properties such as ultimate stress of inactive rat tibia was lower than that of their walking counterparts. Of note, the additive effect of inactivity and OVX was seen only in a few parameters, such as the cancellous bone mineral density of the lumbar vertebrae and the structural parameters of cancellous bone in the lumbar vertebrae/tibiae. It is concluded that the lack of daily activity is detrimental to the strength and quality of cortical bone in the femur and tibia of rats, while lack of estrogen is not. Our inactive rat model, with the older rats, will aid the study of postmenopausal osteoporosis, the etiology of which may be both hormonal and mechanical

Nanosized Hydroxyapatite Coating on PEEK Implants Enhances Early Bone Formation : A Histological and Three-Dimensional Investigation in Rabbit Bone

Polyether ether ketone (PEEK) has been frequently used in spinal surgery with good clinical results. The material has a low elastic modulus and is radiolucent. However, in oral implantology PEEK has displayed inferior ability to osseointegrate compared to titanium materials. One idea to reinforce PEEK would be to coat it with hydroxyapatite (HA), a ceramic material of good biocompatibility. In the present study we analyzed HA-coated PEEK tibial implants via histology and radiography when following up at 3 and 12 weeks. Of the 48 implants, 24 were HA-coated PEEK screws (test) and another 24 implants served as uncoated PEEK controls. HA-coated PEEK implants were always osseointegrated. The total bone area (BA) was higher for test compared to control implants at 3 (p &lt; 0.05) and 12 weeks (p &lt; 0.05). Mean bone implant contact (BIC) percentage was significantly higher (p = 0.024) for the test compared to control implants at 3 weeks and higher without statistical significance at 12 weeks. The effect of HA-coating was concluded to be significant with respect to early bone formation, and HA-coated PEEK implants may represent a good material to serve as bone anchored clinical devices

Single-Cell RNA-Sequencing Reveals the Breadth of Osteoblast Heterogeneity

The current paradigm of osteoblast fate is that the majority undergo apoptosis, while some further differentiate into osteocytes and others flatten and cover bone surfaces as bone lining cells. Osteoblasts have been described to exhibit heterogeneous expression of a variety of osteoblast markers at both transcriptional and protein levels. To explore further this heterogeneity and its biological significance, Venus-positive (Venus+) cells expressing the fluorescent protein Venus under the control of the 2.3-kb Col1a1 promoter were isolated from newborn mouse calvariae and subjected to single-cell RNA sequencing. Functional annotation of the genes expressed in 272 Venus+ single cells indicated that Venus+ cells are osteoblasts that can be categorized into four clusters. Of these, three clusters (clusters 1 to 3) exhibited similarities in their expression of osteoblast markers, while one (cluster 4) was distinctly different. We identified a total of 1920 cluster-specific genes and pseudotime ordering analyses based on established concepts and known markers showed that clusters 1 to 3 captured osteoblasts at different maturational stages. Analysis of gene co-expression networks showed that genes involved in protein synthesis and protein trafficking between endoplasmic reticulum (ER) and Golgi are active in these clusters. However, the cells in these clusters were also defined by extensive heterogeneity of gene expression, independently of maturational stage. Cells of cluster 4 expressed Cd34 and Cxcl12 with relatively lower levels of osteoblast markers, suggesting that this cell type differs from actively bone-forming osteoblasts and retain or reacquire progenitor properties. Based on expression and machine learning analyses of the transcriptomes of individual osteoblasts, we also identified genes that may be useful as new markers of osteoblast maturational stages. Taken together, our data show much more extensive heterogeneity of osteoblasts than previously documented, with gene profiles supporting diversity of osteoblast functional activities and developmental fates.HY, SO, and YY were supported in part by the JSPS KAKENHI, Grants-in-Aid for Scientific Research (17K11613 [HY]; 18K17258 [SO]; 18K19647 [YY]). YY was also supported by the Ono Pharmaceutical Foundation. Part of this work was carried out at the Analysis Center of Life Science, Natural Science Center for Basic Research and Development, Hiroshima University

The influence of nano hydroxyapatite coating on osseointegration after extended healing periods

Objective. Studies observing early wound healing periods around dental implants demon-strate an implants ability to enhance osseointegration, the bone-implant interactions for extended healing periods though have not been thoroughly studied. Methods. Twenty threaded titanium alloy (Ti6Al4V, Grade 5) implants were inserted bilaterally, half prepared to impart stable hydroxyapatite nanoparticles onto a sand blasted and acid etched surface (HA) and half with a non-coated control surface with only heat treatment (HT), into eighteen rabbit femurs. At 12 weeks, the bone-implant blocks were retrieved for micro computed tomography (mu CT), histologic processing and histomorphometric evaluation. Results. The bone-to-implant contact for the entire threaded portion of the implant revealed 57.1% (21.0) for the HT group and 38.8% (17.7) for the HA group with a total bone area within the threads 72.5% (13.9) (HT) and 59.7% (12.5) (HA). The 3D reconstructed mu CT image corresponded to the histomorphometric results. Significance. It is suggested that multiple factors such as the change in topography and chemistry may have influenced the outcomes