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This study identifies senescent osteocytes in the femur and tibia of young rodents and explores their role in bone remodeling. The proximity of osteoclasts to senescent osteocytes was observed, which is a new finding. Cultured osteocytes, sorted using a podoplanin antibody in FACS, exhibited osteocytic characteristics and increased senescence‐related genes. Senescent osteocytes secreted cytokines associated with senescence, remodeling, and inflammation. Notably, IGF1 and MMP2 were elevated in podoplanin‐positive (pdpn+) osteocytes. Migration assays demonstrated significant osteoclast precursor migration towards senescent osteocytes, further confirmed by co‐culture experiments leading to osteoclast differentiation. These findings suggest that senescent osteocytes have a pivotal role in initiating bone resorption, with recruitment of osteoclast precursors during early bone remodeling stages. In conclusion, our research enhances our understanding of complicated bone remodeling mechanisms and bone homeostasis. [ABSTRACT FROM AUTHOR]

We fabricated a microfluidic chip (osteoblast [OB]–osteoclast [OC] chip) that could regulate the mixture amounts of OB and OC supernatants to investigate the effect of different supernatant distributions on osteogenesis or osteoclastogenesis. Computer-aided design was used to produce an OB–OC chip from polydimethylsiloxane. A pressure controller was assembled and different blends of OB and OC supernatants were correctly determined. OB and OC supernatants were placed on the upper panels of the OB–OC chip after differentiation for an in vitro evaluation. We then tested the changes in osteogenesis using MC3T3-E1 cells in the middle chambers. We observed that a 75:25 distribution of OB and OC supernatants was the most potent in osteogenesis. We then primed the osteogenic differentiation of MC3T3-E1 cells using an OB–OC mixed supernatant or an OB supernatant alone (supernatant ratios of 75:25 or 100:0, respectively). These cells were placed on the calvarial defect sites of rats. Microcomputed tomography and histological analyses determined a significantly higher bone formation in the group exposed to the OB–OC supernatant at a ratio of 75:25. In this study, we demonstrate the applicability of an OB–OC chip to evaluate the effect of different supernatant distributions of OB and OC. We observed that the highest bone-forming potential was in MC3T3-E1 cells treated with conditioned media, specifically the OB–OC supernatant at a ratio of 75:25. [ABSTRACT FROM AUTHOR]

The nuclear receptor subfamily 4 group A member 1 (NR4A1) gene plays a crucial role in both osteoporosis and adipogenesis. The present study investigated the mechanisms by which NR4A1 influences osteoblastogenesis and adipogenesis in human bone marrow-derived mesenchymal stem cells (BMD-MSCs). NR4A1 was overexpressed or knocked down in mouse MC3T3-E1 osteoblast cells and 3T3-L1 adipocyte cells, as well as in PCS-500-012, a BMD-MSC line. The alkaline phosphatase (ALP) assay and Alizarin Red S staining were performed using MC3T3-E1 and BMD-MSCs to assess ALP activity and mineralization, while Oil Red O staining was used to assess the lipid content in 3T3-L1 cells and BMD-MSCs. Total RNA was isolated from control, NR4A1-overexpressing and NR4A1 small interfering RNA (siRNA; siNR4A1)-treated BMD-MSCs. RNA sequencing (RNA-seq) was performed to identify differentially expressed genes, followed by ingenuity pathway analysis (IPA) to determine the role of NR4A1 in osteoblastogenesis and adipogenesis. NR4A1 or Nr4a1 knockdown tended to increase ALP activity and significantly increased calcification in BMD-MSCs (P<0.005) and MC3T3-E1 cells (P<0.005), respectively. By contrast, NR4A1 or Nr4a1 overexpression significantly decreased ALP activity and calcification. NR4A1 or Nr4a1 knockdown and overexpression significantly decreased and increased adipogenesis, respectively, in BMD-MSCs (P<0.005 and <0.05, respectively) and 3T3-L1 cells (P<0.005 in both). Treatments of BMD-MSCs with an NR4A1 antagonist, 1,1-bis(3′-indolyl)-1-(p-hydroxyphenyl) methane and siNR4A1 showed similar results. RNA-seq and IPA in control, NR4A1 knockdown and NR4A1 overexpressing cells indicated that Notch signaling mediated the effects of NR4A1 in osteoblastogenesis and adipogenesis. Expression of mastermind-like transcriptional coactivator 3 was reduced in the Notch signaling pathway in cells treated with siNR4A1. In conclusion, NR4A1 suppressed osteoblastogenesis and promotes adipogenesis in human BMD-MSCs. The present study also suggested that NR4A1 plays a role in the progression of osteoporosis and adipogenesis by modulating the Notch signaling cascade. [ABSTRACT FROM AUTHOR]

The systemic gene interactions that occur during osteoporosis and their underlying mechanisms remain to be determined. To this end, mesenchymal stromal cells (MSCs) were analyzed from bone marrow samples collected from healthy individuals (n = 5) and patients with osteoporosis (n = 5). A total of 120 osteoporosis-related genes were identified using RNA-sequencing (RNA-seq) and Ingenuity Pathway Analysis (IPA) software. In order to analyze these genes, we constructed a heatmap of one-way hierarchical clustering and grouped the gene expression patterns of the samples. The MSCs from one control participant showed a similar expression pattern to that observed in the MSCs of three patients with osteoporosis, suggesting that the differentiating genes might be important genetic determinants of osteoporosis. Then, we selected the top 38 genes based on fold change and expression, excluding osteoporosis-related genes from the control participant. We identified a network among the top 38 genes related to osteoblast and osteoclast differentiation, bone remodeling, osteoporosis, and sarcopenia using the Molecule Activity Predictor program. Among them, 25 genes were essential systemic genes involved in osteoporosis. Furthermore, we identified 24 genes also associated with diabetes and obesity, among which 10 genes were involved in a network related to bone and energy metabolism. The study findings may have implications for the treatment and prevention of osteoporosis. [ABSTRACT FROM AUTHOR]

Petrophysical properties of volcanic rocks are controlled by lithology and subsequent modification by alteration processes. Investigating the linkages, using a range of different techniques, are important to establish how petrophysical properties can inform about the alteration state of volcanic rocks. Here, we compile petrophysical data and correlate these with geochemical and mineralogical analyses acquired from a volcanic sequence on the Naturaliste Plateau, offshore southwest Australia (International Ocean Discovery Program Site U1513). The sequence consists of alternating basalt lava flows and volcaniclastic deposits, intruded by multiple dolerite dikes. Variable alteration intensities from fresh‐slight to strong are quantified using Chemical Index of Alteration. Intervals of slightly altered dikes exhibit low porosity and high values of bulk density, P‐wave velocity, and thermal conductivity. The increase of alteration intensity corresponds to decreases in bulk density to ∼2 g/cm3, P‐wave velocity to ∼2,000 m/s, thermal conductivity to ∼1.2 W/(m·K) and an increase in porosity up to 50%. Natural Gamma Ray and magnetic susceptibility vary downhole with rock composition and at lithologic boundaries. The distinct variations exhibit a good correlation with primary lithologic characteristics and secondary mineralogical and textural changes attributed to alteration processes. We provide synthesis models of petrophysical variation with alteration intensity. Although differences in primary lithology and alteration type introduce limitations and uncertainties, there is a reasonable applicability of our results to rapidly characterize the alteration intensity and volcanic stratigraphy in volcanic sequences and to calibrate wireline log‐based determinations. This will help others to develop strategies for exploration, drilling, and geophysical research of volcanic rocks. Plain Language Summary: We present the physical properties of rocks comprising a volcanic sequence recovered from the eastern Naturaliste Plateau, offshore southwest Australia. The sequence consists of basalt lava flows and volcaniclastic deposits, which are intruded by multiple dikes. Petrophysical properties of the volcanic rocks are variable with lithology and alteration state. To investigate the linkages, we applied a range of different techniques to correlate petrophysical data with geochemical and mineralogical analyses. The alteration intensity was quantified based on chemical composition into four ranges; fresh‐slight, weak, moderate, and strong. Relatively fresh basalt intervals exhibit low porosity and high values of bulk density, P‐wave velocity, and thermal conductivity. Increases of alteration intensity correspond to decreases in bulk density to ∼2 g/cm3, P‐wave velocity to ∼2,000 m/s, thermal conductivity to ∼1.2 W/(m·K), and an increase in porosity up to 50%. Natural Gamma Ray and magnetic susceptibility vary with rock composition and at lithologic boundaries. The petrophysical variations were associated with primary lithologic characteristics, secondary mineralogical and textural changes. We provide synthesis models of petrophysical variation with alteration intensity. Our results can be used to rapidly characterize the alteration intensity and volcanic stratigraphy in volcanic sequences and to develop strategies for exploration, drilling, and research of volcanic rocks. Key Points: Petrophysical properties of a volcanic sequence at International Ocean Discovery Program Site U1513 on the Naturaliste Plateau were modified by alteration processesDistinct trends are indicated in correlations of petrophysical variations with alteration intensity and lithologic characteristicsThis study provides synthesis models of petrophysical parameters corresponding to alteration intensity [ABSTRACT FROM AUTHOR]

A critically tapered active accretionary wedge was simulated using a numerical analysis of plastic slip-line theory to understand the mechanics of morphologic evolution. The concept of critical state soil mechanics was applied to describe the entire wedge area overlying a basal décollement fault. Presuming a condition of two-dimensional plane strain along the compressional direction, we obtained the numerical solution of conjugate plastic slip lines at a critical state of stress defined by the Coulomb yield criterion. The velocity vectors were obtained by applying the associate flow rule with the boundary conditions at the upper surface of the wedge. Finally, the detachment was determined from the effective stress condition inside the wedge and the sliding friction coefficient along the fault. Our numerical simulations demonstrate that the morphology of a critically tapered wedge is dependent on the frictional strengths of both the wedge materials and the basal fault. The critical taper angle decreases with increasing internal friction angle and decreasing basal friction coefficient. The results also revealed that the pore pressure controls the morphology of the accretionary wedge for cohesive sediments but not for non-cohesive materials. The effect of pore pressure on the morphology of a critically tapered accretionary wedge becomes more significant as the cohesion increases. Assuming that the cohesion is very low, we could infer the ranges of strengths that most observed wedge geometry data have 0.3–0.6 for the basal friction coefficient and ~35–45° for the internal friction angle of the wedge materials. [ABSTRACT FROM AUTHOR]

Genetic alterations are major contributing factors in the development of osteoporosis. Osteoblasts and adipocytes share a common origin, mesenchymal stem cells (MSCs), and their genetic determinants might be important in the relationship between osteoporosis and obesity. In the present study, we aimed to isolate differentially expressed genes (DEGs) in osteoporosis and normal controls using human MSCs, and elucidate the common pathways and genes related to osteoporosis and adipogenesis. Human MSCs were obtained from the bone marrow of femurs from postmenopausal women during orthopedic surgeries. RNA sequencing (RNA-seq) was carried out using next-generation sequencing (NGS) technology. DEGs were identified using RNA-seq data. Ingenuity pathway analysis (IPA) was used to elucidate the common pathway related to osteoporosis and adipogenesis. Candidate genes for the common pathway were validated with other independent osteoporosis and obese subjects using RT-PCR (reverse transcription-polymerase chain reaction) analysis. Fifty-three DEGs were identified between postmenopausal osteoporosis patients and normal bone mineral density (BMD) controls. Most of the genetic changes were related to the differentiation of cells. The nuclear receptor subfamily 4 group A (NR4A) family was identified as possible common genes related to osteogenesis and adipogenesis. The expression level of the mRNA of NR4A1 was significantly higher in osteoporosis patients than in controls (p = 0.018). The expression level of the mRNA of NR4A2 was significantly higher in obese patients than in controls (p = 0.041). Some genetic changes in MSCs are involved in the pathophysiology of osteoporosis. The NR4A family might comprise common genes related to osteoporosis and obesity. [ABSTRACT FROM AUTHOR]

This brief introduces a variable step-size (VSS) normalized subband adaptive filter (NSAF) using a step-size scaler to improve the robustness against impulsive measurement noise. When impulsive measurement noise appears, the step size of the proposed VSS NSAF is scaled down by the step-size scaler, which is suitable for application in the NSAF. This removes a possibility of updating weight estimates based on defective information of the subband output errors due to impulsive measurement noise. In the proposed VSS NSAF, the equations for updating the step size are constructed by interpreting the behavior of the mean square deviation of the conventional NSAF and applying the step-size scaler. The step-size scaler utilizes the sum of the subband output errors, which can be influenced by impulsive measurement noise. Simulations using the proposed VSS NSAF show an excellent transient and steady-state behavior with colored input in impulsive-noise environments. [ABSTRACT FROM AUTHOR]

This paper proposes a novel robust affine projection sign algorithm (R-APSA) through a modified criterion that consists of the Euclidean norm of the sum of the difference between the present weight vector and the previous weight vectors. Because the filter update equation of the proposed R-APSA is obtained from the modified criterion, it has robustness against the high power of measurement noises. Moreover, due to the characteristic inherent in the original APSA, the proposed R-APSA performs well even though impulsive noises occur. Simulation results verify that the proposed R-APSA attains smaller steady-state errors than the existing released algorithms. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

This letter proposes a variable step-size (VSS) affine projection algorithm (APA) associated with a step-size scaler to improve the APA's robustness against impulsive measurement noise. In the proposed VSS APA, the step-size scaler is applied to the equations for updating the step size, which are developed by interpreting the behavior of the mean square deviation (MSD) of the conventional APA. To reduce the computational complexity, we also propose a simplified version of the step-size scaler, which is suitable for application in the APA. Simulations show that the proposed algorithm leads to an excellent transient and steady-state behavior with colored inputs in impulsive-noise environments. [ABSTRACT FROM AUTHOR]

This brief introduces the concept of a step-size scaler by investigating and modifying the \tanh cost function for adaptive filtering with impulsive measurement noise. The step-size scaler instantly scales down the step size of gradient-based adaptive algorithms whenever impulsive measurement noise appears, which eliminates a possibility of updating weight vector estimates based on wrong information due to impulsive noise. The most attractive feature of the step-size scaler is that this is easily applicable to various gradient-based adaptive algorithms. Several representative gradient-based adaptive algorithms are performed without or with the step-size scaler in impulsive-noise environments, which shows the improvement of robustness against impulsive noise. [ABSTRACT FROM AUTHOR]

Abstract: We studied the effect of bone morphogenetic protein-2 (BMP-2) and vitamin D3 on the osteogenic differentiation of adipose stem cells (ASCs). ASCs were treated with 10, 50, and 100ng/ml of BMP-2, and 10−8, 10−7, 10−6 M vitamin D3. Then, to investigate the effects of combined treatment, ASCs were treated with BMP-2 and vitamin D3 dose-dependently and time-dependently. The osteogenic differentiation was assessed by alkaline phosphatase (ALP) activities/staining and the mineralization was evaluated by Alizarin red S staining. ALP activity and mineralization dose-dependently increased in early stages (ALP on 7th day and mineralization on the 14th day) while all three doses of BMP-2 or vitamin D3 showed comparable effects in late stages (ALP on the 14th day and mineralization on the 21st day) in ASCs. BMP-2 and vitamin D3 had synergistic effect on the osteogenic differentiation of ASCs. While all three doses of BMP-2 acted similarly in reinforcing the effect of vitamin D3, vitamin D3 dose-dependently augmented the osteogenic effect of BMP-2. When BMP-2 was constantly treated, vitamin D3 effect did not differ depending on the period of vitamin D3 treatment. However, when vitamin D3 was constantly treated, the BMP was more effective when treated for the last 7days than when treated for the first 7days. In conclusion, BMP-2 and vitamin D3 promote osteogenic differentiation of ASCs, and can work synergistically. These results can be used to induce effective and economical osteogenic induction of ASCs for bone tissue engineering. [Copyright &y& Elsevier]

Abstract: NFATc1 is a master regulator of RANKL-induced osteoclast differentiation and herein we investigate the regulatory mechanism of NFATc1 in osteoclast activation. Inactivation of NFATc1 strongly attenuates RANKL-induced bone resorption and overexpression of a constitutively active form of NFATc1 in osteoclasts induces formation of actin rings and resorption pits on dentin slices. We demonstrate that NFATc1 binds directly to the promoter regions of its target genes and induces expression of various genes, including LTBP3, ClC7, cathepsin K, MMP9, and c-Src, which are key players in bone resorption. Thus, NFATc1 is essential for RANKL-induced osteoclast activation via up-regulation of osteoclast-activating genes. [Copyright &y& Elsevier]

Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic approach for diverse diseases and injuries. The biological and clinical advantages of human fetal MSCs (hfMSCs) have recently been reported. In terms of promising therapeutic approaches for diverse diseases and injuries, hfMSCs have gained prominence as healing tools for clinical therapies. Therefore, this review assesses not the only biological advantages of hfMSCs for healing human diseases and regeneration, but also the research evidence for the engraftment and immunomodulation of hfMSCs based on their sources and biological components. Of particular clinical relevance, the present review also suggests the potential therapeutic feasibilities of hfMSCs for musculoskeletal disorders, including osteoporosis, osteoarthritis, and osteogenesis imperfecta. [ABSTRACT FROM AUTHOR]

Oscillatory hydraulic tests were conducted on samples of two varieties of Fontainebleau sandstone differing in porosity and a stacked sample of the two varieties. Simultaneous measurements of the upstream and downstream pressures and the upstream fluid flow permit the calculation of permeability and specific storage by two methods, the conventional upstream–downstream pressure analysis and the upstream pressure-flow analysis. The pressure analysis yields a relatively constant permeability for the high-porosity sample at different effective pressures and oscillation periods, but slightly period-dependent permeability for the low-porosity samples and the stacked sample. The period dependence diminishes with increasing period. Estimates of specific storage capacity derived from pressure analysis appear problematic. For samples with the higher porosity, values are highly uncertain due to peculiarities of the solution space used to convert attenuation and phase shift to permeability and storage capacity. For the sample with the lower porosity and the stacked sample, normalized storage capacity values fall significantly below the physical limit constituted by sample porosity. The flow analysis yields well-constrained values of permeability and specific storage capacity for the sample with the higher porosity. For the samples with the lower porosity and the stacked sample, both parameters show a strong dependence on oscillation period. We suppose that the two methods probe different portions of the pore space and thus yield different results for heterogeneous samples when periods fall below a critical period estimated from the scaling relation for hydraulic diffusivity. Flow analysis probes the portion of the sample facing the upstream reservoir with a thickness approximated by the penetration depth. In contrast, the pressure analysis probes the dominant flow path connecting the sample ends. In samples with connected but stagnant pores, the storage capacity has two distinct contributions from an effectively storing porosity and an effectively conducting porosity. The observed period dependence of storage capacity probably reflects the shift in balance between the two contributors. [ABSTRACT FROM AUTHOR]

Abstract: Breakouts observed in a vertical borehole (C0002A) drilled through two major tectonic sedimentary formations consisting of forearc basin (upper) and accretionary prism (lower) sediments in the Nankai accretionary wedge, Japan, exhibit distinctive geometric features in respective formations. Breakouts in the lower accretionary prism sediments are markedly wider than those in the forearc basin sediments, and breakout azimuths in the two units are horizontally rotated relative to one another. Breakout azimuths are widely used as a proxy for the determination of principal stress directions. However, strength anisotropies related to the presence of bedding planes may affect both breakout azimuths and widths, which can result in misleading in situ stress interpretations. While thinly bedded mudstones are the dominant lithology in both the forearc basin and accretionary prism sediments, bedding planes in the accretionary prism sediments are relatively steeper than those in the forearc basin sediments, with possible implications for breakout geometry and interpretations of principal stress directions. To investigate the effects of bedding planes on breakout geometry (azimuth and width), we conducted borehole wall failure analyses using a weak-plane failure model that incorporates material strength anisotropies. The model results show that breakout widths and orientations are strongly affected by steeply dipping (>40°) bedding planes in cases where dip directions are unaligned with the principal stress orientation. Our theoretical results suggest that variations in breakout azimuths in the C0002A site may be associated with bedding plane related strength anisotropy, and not associated with the rotation of stress field. That is, stress orientation is consistent throughout the borehole (down to the bottom-hole depth of 1495 m below sea floor). In addition, disregarding the effects of bedding planes tends to yield an overestimation of in situ stress magnitude. [Copyright &y& Elsevier]