Increased Bone Resorption during Lactation in Pycnodysostosis

Pycnodysostosis, a rare autosomal recessive skeletal dysplasia, is caused by a deficiency of cathepsin K. Patients have impaired bone resorption in the presence of normal or increased numbers of multinucleated, but dysfunctional, osteoclasts. Cathepsin K degrades collagen type I and generates N-telopeptide (NTX) and the C-telopeptide (CTX) that can be quantified. Levels of these telopeptides are increased in lactating women and are associated with increased bone resorption. Nothing is known about the consequences of cathepsin K deficiency in lactating women. Here we present for the first time normalized blood and CTX measurements in a patient with pycnodysostosis, exclusively related to the lactation period. In vitro studies using osteoclasts derived from blood monocytes during lactation and after weaning further show consistent bone resorption before and after lactation. Increased expression of cathepsins L and S in osteoclasts derived from the lactating patient suggests that other proteinases could compensate for the lack of cathepsin K during the lactation period of pycnodysostosis patients.     

Targeting Intercellular Communication in the Bone Microenvironment to Prevent Disseminated Tumor Cell Escape from Dormancy and Bone Metastatic Tumor Growth

Metastasis to the bone is a common feature of many cancers including those of the breast, prostate, lung, thyroid and kidney. Once tumors metastasize to the bone, they are essentially incurable. Bone metastasis is a complex process involving not only intravasation of tumor cells from the primary tumor into circulation, but extravasation from circulation into the bone where they meet an environment that is generally suppressive of their growth. The bone microenvironment can inhibit the growth of disseminated tumor cells (DTC) by inducing dormancy of the DTC directly and later on following formation of a micrometastatic tumour mass by inhibiting metastatic processes including angiogenesis, bone remodeling and immunosuppressive cell functions. In this review we will highlight some of the mechanisms mediating DTC dormancy and the complex relationships which occur between tumor cells and bone resident cells in the bone metastatic microenvironment. These inter-cellular interactions may be important targets to consider for development of novel effective therapies for the prevention or treatment of bone metastases.     

Stretchable,Antifreezing, Non-Drying,and Fast-Response Sensors Based on Cellulose Nanocomposite Hydrogels for Signal Detection

Conductive hydrogels have received widespread attention in the applications of biosensors, human–machine interface, and health recording electrodes. Herein, the conductive hydrogels integrated with antifreezing, water retention, reusable, and sensing performances are fabricated by introducing polyvinyl alcohol, cellulose nanofibril, MXene nanosheets, and glycerol. The as-prepared hydrogels present prominent electrical conductivity (2.58 mS cm⁻¹) and flexibility even at −18 °C. In addition, the hydrogels have favorable water retention performance and can reuse after heating and cooling. When used as sensors, the hydrogels illustrate high sensitivity (gauge factor of 2.30), fast response time (0.165 s), wide working strain range (559%), favorable linearity (R² = 0.999), and wide operating temperature range (−18 to 60 °C). The hydrogels can detect not only large strains of 10–200%, but also small strains of 1–5%, making them promising candidates for wearable sensors to monitor large and subtle movements.     

Fractional Order Nonlinear Bone Remodeling Dynamics Using the Supervised Neural Network

This study aims to solve the nonlinear fractional-order mathematical model (FOMM) by using the normal and dysregulated bone remodeling of the myeloma bone disease (MBD). For the more precise performance of the model, fractional-order derivatives have been used to solve the disease model numerically. The FOMM is preliminarily designed to focus on the critical interactions between bone resorption or osteoclasts (OC) and bone formation or osteoblasts (OB). The connections of OC and OB are represented by a nonlinear differential system based on the cellular components, which depict stable fluctuation in the usual bone case and unstable fluctuation through the MBD. Untreated myeloma causes by increasing the OC and reducing the osteoblasts, resulting in net bone waste the tumor growth. The solutions of the FOMM will be provided by using the stochastic framework based on the Levenberg-Marquardt backpropagation (LVMBP) neural networks (NN), i.e., LVMBPNN. The mathematical performances of three variations of the fractional-order derivative based on the nonlinear disease model using the LVMPNN. The static structural performances are 82% for investigation and 9% for both learning and certification. The performances of the LVMBPNN are authenticated by using the results of the Adams-Bashforth-Moulton mechanism. To accomplish the capability, steadiness, accuracy, and ability of the LVMBPNN, the performances of the error histograms (EHs), mean square error (MSE), recurrence, and state transitions (STs) will be provided.     

Extracting 3D information on bone remodeling in the proximity of titanium implants in SRμCT image volumes

Bone-implant integration is measured in several ways. Traditionally and routinely, 2D histological sections of samples, containing bone and the biomaterial, are stained and analyzed using a light microscope. Such histological section provides detailed cellular information about the bone regeneration in the proximity of the implant. However, this information reflects the integration in only a very small fraction, a 10 μm thick slice, of the sample. In this study, we show that feature values quantified on 2D sections are highly dependent on the orientation and the placement of the section, suggesting that a 3D analysis of the whole sample is of importance for a more complete judgment of the bone structure in the proximity of the implant. We propose features describing the 3D data by extending the features traditionally used for 2D-analysis. We present a method for extracting these features from 3D image data and we measure them on five 3D SRμCT image volumes.We also simulate cuts through the image volume positioned at all possible section positions. These simulations show that the measurement variations due to the orientation of the section around the center line of the implant are about 30%.     

反求原理在重构模具自由曲面中的应用

以某一实际自由曲面为例，结合三坐标测量机(LK G90CSl5．10．8)的特点，在实际反求工作中采用该三坐标测量机对自由曲面进行扫描测量，对测量数据进行预先处理，应用三角Bezier原理．编程实现曲面重构，得到曲面CAD模型．     

Endogenous Modulation of Extracellular Matrix Collagen during Scar Formation after Myocardial Infarction

Myocardial infarction is remains the leading cause of death in developed countries. Recent data show that the composition of the extracellular matrix might differ despite similar heart function and infarction sizes. Because collagen is the main component of the extracellular matrix, we hypothesized that changes in inflammatory cell recruitment influence the synthesis of different collagen subtypes in myofibroblasts, thus changing the composition of the scar. We found that neutrophils sustain the proliferation of fibroblasts, remodeling, differentiation, migration and inflammation, predominantly by IL-1 and PPARγ pathways (n = 3). They also significantly inhibit the mRNA expression of fibrillar collagen, maintaining a reduced stiffness in isolated myofibroblasts (n = 4–5). Reducing the neutrophil infiltration in CCR1^−/− resulted in increased mRNA expression of collagen 11, moderate expression of collagen 19 and low expression of collagen 13 and 26 in the scar 4 weeks post infarction compared with other groups (n = 3). Mononuclear cells increased the synthesis of all collagen subtypes and upregulated the NF-kB, angiotensin II and PPARδ pathways (n = 3). They increased the synthesis of collagen subtypes 1, 3, 5, 16 and 23 but reduced the expression of collagens 5 and 16 (n = 3). CCR2^−/− scar tissue showed higher levels of collagen 13 (n = 3), in association with a significant reduction in stiffness (n = 4–5). Upregulation of the inflammation-related genes in myofibroblasts mostly modulated the fibrillar collagen subtypes, with less effect on the FACIT, network-forming and globular subtypes (n = 3). The upregulation of proliferation and differentiation genes in myofibroblasts seemed to be associated only with the fibrillar collagen subtype, whereas angiogenesis-related genes are associated with fibrillar, network-forming and multiplexin subtypes. In conclusion, although we intend for our findings to deepen the understanding of the mechanism of healing after myocardial infarction and scar formation, the process of collagen synthesis is highly complex, and further intensive investigation is needed to put together all the missing puzzle pieces in this still incipient knowledge process.     

Effects of Loganin on Bone Formation and Resorption In Vitro and In Vivo

Osteoporosis is a disease caused by impaired bone remodeling that is especially prevalent in elderly and postmenopausal women. Although numerous chemical agents have been developed to prevent osteoporosis, arguments remain regarding their side effects. Here, we demonstrated the effects of loganin, a single bioactive compound isolated from Cornus officinalis, on osteoblast and osteoclast differentiation in vitro and on ovariectomy (OVX)-induced osteoporosis in mice in vivo. Loganin treatment increased the differentiation of mouse preosteoblast cells into osteoblasts and suppressed osteoclast differentiation in primary monocytes by regulating the mRNA expression levels of differentiation markers. Similar results were obtained in an osteoblast–osteoclast co-culture system, which showed that loganin enhanced alkaline phosphatase (ALP) activity and reduced TRAP activity. In in vivo experiments, the oral administration of loganin prevented the OVX-induced loss of bone mineral density (BMD) and microstructure in mice and improved bone parameters. In addition, loganin significantly increased the serum OPG/RANKL ratio and promoted osteogenic activity during bone remodeling. Our findings suggest that loganin could be used as an alternative treatment to protect against osteoporosis.     

Osteoporosis Preclinical Research: A Systematic Review on Comparative Studies Using Ovariectomized Sheep

Sheep ovariectomy (OVX) alone or associated to steroid therapy, deficient diet, or hypothalamic–pituitary disconnection has proven to be of critical importance for osteoporosis research in orthopedics. However, the impact of specific variables, such as breed, age, diet, time after OVX, and other variables, should be monitored. Thus, the design of comparative studies is mandatory to minimize the impact of these variables or to recognize the presence of unwanted variables as well as to better characterize bone remodeling in this model. Herein, we conducted a systematic review of the last 10 years on PubMed, Scopus, and Web of Knowledge considering only studies on OVX sheep where a control group was present. Of the 123 records screened, 18 studies were included and analyzed. Results showed that (i) Merino sheep are the most exploited breed; (ii) 5–6 years of age is the most used time for inducing OVX; (iii) ventral midline laparotomy is the most common approach to induce OVX; (iv) OVX associated to steroid therapy is the most widely used osteoporosis model; and (v) success of OVX was mostly verified 12 months after surgery. In detail, starting from 12 months after OVX a significant decline in bone mineral density and in microarchitectural bone parameters as well as in biochemical markers were detected in all studies in comparison to control groups. Bone alteration was also site-specific on a pattern as follows: lumbar vertebra, femoral neck, and ribs. Before 12 months from OVX and starting from 3–5 months, microarchitectural bone changes and biochemical marker alterations were present when osteoporosis was induced by OVX associated to steroid therapy. In conclusion, OVX in sheep influence bone metabolism causing pronounced systemic bone loss and structural deterioration comparable to the situation found in osteoporosis patients. Data for treating osteoporosis patients are based not only on good planning and study design but also on a correct animal use that, as suggested by 3Rs principles and by ARRIVE guidelines, includes the use of control groups to be directly contrasted with the experimental group.