Micro CT analysis of the subarticular bone structure in the area of the talar trochlea

Purpose: Certain regions of the talar trochlea are recognized as exhibiting varying cartilage thickness and degrees of subchondral bone mineralization. These changes have been attributed to the long-term loading history. For the current study, we accepted the hypothesis that stress-induced alterations of the joint surface include not only varying degrees of subchondral lamellar mineralization, but also structural changes of the subarticular cancellous bone. Methods: In order to examine the structure of the subarticular cancellous bone, ten formalin-fixed talar trochleae were analyzed using micro CT. Sixteen measurement zones were defined and then evaluated in five layers each of 1-mm thickness, enabling assessment of the cancellous architecture extending 5mm below the trochlear surface using numerical and structural parameters. Results: As with mineralization patterns in the subchondral lamella, large variation was observed regarding bone volume, trabecular quantity, thickness, and spacing, as well as for structure model index and degree of anisotropy, depending on localization. In addition, like previous reports examining mineralization of the subchondral lamella, two distinct groups could be identified as "bicentric” or "monocentric”. Conclusions: These results show that structural tissue adaptation probably due to loading history is also evident within the subarticular cancellous bon

X-ray micro computed tomography for the visualization of an atherosclerotic human coronary artery

Atherosclerosis refers to narrowing or blocking of blood vessels that can lead to a heart attack, chest pain or stroke. Constricted segments of diseased arteries exhibit considerably increased wall shear stress, compared to the healthy ones. One of the possibilities to improve patient's treatment is the application of nano-therapeutic approaches, based on shear stress sensitive nano-containers. In order to tailor the chemical composition and subsequent physical properties of such liposomes, one has to know precisely the morphology of critically stenosed arteries at micrometre resolution. It is often obtained by means of histology, which has the drawback of offering only two-dimensional information. Additionally, it requires the artery to be decalcified before sectioning, which might lead to deformations within the tissue. Micro computed tomography (muCT) enables the three-dimensional (3D) visualization of soft and hard tissues at micrometre level. muCT allows lumen segmentation that is crucial for subsequent flow simulation analysis. In this communication, tomographic images of a human coronary artery before and after decalcification are qualitatively and quantitatively compared. We analyse the cross section of the diseased human coronary artery before and after decalcification, and calculate the lumen area of both samples

The Role of T Lymphocytes in Skeletal Muscle Repair From Traumatic and Contraction-Induced Injury

Skeletal muscle is prone to damage from a range of stimuli, and initiates a robust repair process that requires the participation of immune cells. Among the more well characterized immune cells involved in muscle repair are those of the myeloid lineage, including neutrophils, macrophages, monocytes, and eosinophils. More recently, studies have begun to elucidate the role of the lymphoid-derived immune cells, most notably T lymphocytes (T-cells), in the complex processes of muscle repair. Though T-cells have been traditionally been associated with pathological degeneration of skeletal muscle in disease, recent studies show that T-cells are instrumental in the repair/regeneration process following severe muscle damage in mice. Furthermore, a few studies using basic immunohistochemical assays have shown that T-cells accumulate in human skeletal muscle in the days following contraction-induced muscle damage. The functional significance of T-cells in the repair and adaptation process following contraction-induce muscle damage remains uncertain, and is an active area of intense investigation. This mini-review summarizes recent findings on the involvement of T-cells in skeletal muscle repair

Stimulated Muscle Contractions Regulate Membrane-Bound and Soluble TLR4 to Prevent LPS-Induced Signaling and Myotube Atrophy in Skeletal Muscle Cells

Toll-like receptor 4 (TLR4) activation by lipopolysaccharides (LPS) contributes to chronic inflammation and causes upregulation of muscle atrophy signaling pathways. Exercise can suppress LPS/TLR4 axis activation by reducing the expression of TLR4 on immune cells. It is unknown how this regulation occurs, and it is not clear how exercise affects TLR4 on skeletal muscle. PURPOSE: To uncover the nature and mechanisms by which exercise affects TLR4 expression and intracellular signaling using cell culture models and human experiments. METHODS: C2C12 myotubes were subjected to electrical pulse stimulation (EPS) with and without subsequent treatment with 500 ng/mL lipopolysaccharide (LPS) along with corresponding control conditions. To investigate the effect of muscle contraction on the regulation of TLR4 in-vivo, we analyzed PBMC and serum samples from eight recreationally active men that completed 60-minutes of cycling at a moderate intensity (65% of VO2max). RESULTS: In-vitro, LPS decreased membrane-bound TLR4, increased TLR4 signaling (decreased inhibitor of κBα), and induced myotube atrophy. However, stimulated muscle contractions decreased membrane-bound TLR4, increased soluble TLR4 (sTLR4), and prevented LPS-induced signaling and myotube atrophy. In human participants, a single bout of moderate-intensity exercise decreased membrane-bound TLR4 on PBMCs and increased serum-borne sTLR4. CONCLUSION: These experiments support exercise may exert a novel anti-catabolic/ anti-inflammatory effect by increasing sTLR4 and decreasing TLR4 expressed on the muscle membrane. These results could help improve interventions for conditions associated with TLR4-mediated inflammation and muscle atrophy, such as diabetes, sarcopenia, and cancer cachexia

Comparative analysis of bone structural parameters reveals subchondral cortical plate resorption and increased trabecular bone remodeling in human facet joint osteoarthritis

Facet joint osteoarthritis is a prominent feature of degenerative spine disorders, highly prevalent in ageing populations, and considered a major cause for chronic lower back pain. Since there is no targeted pharmacological therapy, clinical management of disease includes analgesic or surgical treatment. The specific cellular, molecular, and structural changes underpinning facet joint osteoarthritis remain largely elusive. The aim of this study was to determine osteoarthritis-related structural alterations in cortical and trabecular subchondral bone compartments. To this end, we conducted comparative micro computed tomography analysis in healthy (n = 15) and osteoarthritic (n = 22) lumbar facet joints. In osteoarthritic joints, subchondral cortical plate thickness and porosity were significantly reduced. The trabecular compartment displayed a 42 percent increase in bone volume fraction due to an increase in trabecular number, but not trabecular thickness. Bone structural alterations were associated with radiological osteoarthritis severity, mildly age-dependent but not gender-dependent. There was a lack of association between structural parameters of cortical and trabecular compartments in healthy and osteoarthritic specimens. The specific structural alterations suggest elevated subchondral bone resorption and turnover as a potential treatment target in facet joint osteoarthritis

The DIAD Approach to Correlative Synchrotron X‑ray Imaging and Diffraction Analysis of Human Enamel

The Dual Imaging and Diffraction (DIAD) beamline at Diamond Light Source (Didcot, U.K.) implements a correlative approach to the dynamic study of materials based on concurrent analysis of identical sample locations using complementary X-ray modalities to reveal structural detail at various length scales. Namely, the underlying beamline principle and its practical implementation allow the collocation of chosen regions within the sample and their interrogation using real-space imaging (radiography and tomography) and reciprocal space scattering (diffraction). The switching between the two principal modes is made smooth and rapid by design, so that the data collected is interlaced to obtain near-simultaneous multimodal characterization. Different specific photon energies are used for each mode, and the interlacing of acquisition steps allows conducting static and dynamic experiments. Building on the demonstrated realization of this state-of-the-art approach requires further refining of the experimental practice, namely, the methods for gauge volume collocation under different modes of beam–sample interaction. To address this challenge, experiments were conducted at DIAD devoted to the study of human dental enamel, a hierarchical structure composed of hydroxyapatite mineral nanocrystals, as a static sample previously affected by dental caries (tooth decay) as well as under dynamic conditions simulating the process of acid demineralization. Collocation and correlation were achieved between WAXS (wide-angle X-ray scattering), 2D (radiographic), and 3D (tomographic) imaging. While X-ray imaging in 2D or 3D modes reveals real-space details of the sample microstructure, X-ray scattering data for each gauge volume provided statistical nanoscale and ultrastructural polycrystal reciprocal-space information such as phase and preferred orientation (texture). Careful registration of the gauge volume positions recorded during the scans allowed direct covisualization of the data from two modalities. Diffraction gauge volumes were identified and visualized within the tomographic data sets, revealing the underlying local information to support the interpretation of the diffraction patterns. The present implementation of the 4D microscopy paradigm allowed following the progression of demineralization and its correlation with time-dependent WAXS pattern evolution in an approach that is transferable to other material systems

Effect of Maternal Exercise on Adverse Cardio-Pulmonary Responses in Offspring Exposed to Post-Natal Chronic Hypoxia

Emerging evidence shows exercise by women throughout pregnancy (i.e., maternal exercise) endows the offspring with positive health benefits and resistance to many diseases later in life. PURPOSE: To determine if maternal exercise reduces unfavorable cardiopulmonary development and improves exercise capacity in offspring after chronic hypoxic exposure throughout early life. METHODS: Female adult C57BL/6J mice were randomly assigned to one of the following groups: high altitude, sedentary (HS), high altitude, active (HE), or the respective, low-altitude conditions (LS or LE). Pregnant females in the exercise groups performed voluntary wheel running during mating and the perinatal period (about 4 weeks). Three days after birth, the pups in the high-altitude groups were exposed to chronic hypobaric hypoxia (450mmHg). When pups were eight weeks old, body size (weight and tail length) was measured and exercise capacity was assessed via a Rotarod test. Terminal procedures were performed to measure right ventricular systolic pressure (RVSP), hematocrit, and heart remodeling (Fulton’s Index: right ventricular weight ratio to bodyweight (RV/BW) and to the left ventricle plus septum (RV/LV+S)). RESULTS: All variables measured had a main effect for altitude (pCONCLUSION: Chronic hypoxia decreases exercise capacity and attenuates growth. This stress also induces potentially harmful cardiovascular changes, such as high blood viscosity, RVSP, and right ventricular hypertrophy. Our results indicate that maternal exercise may attenuate some of the negative effects of chronic hypoxia in the offspring, but does not prevent significant development impairments

Stem Cell Regulation by Arabidopsis WOX Genes

Gene amplification followed by functional diversification is a major force in evolution. A typical example of this is seen in the WUSCHEL-RELATED HOMEOBOX (WOX) gene family, named after the Arabidopsis stem cell regulator WUSCHEL. Here we analyze functional divergence in the WOX gene family. Members of the WUS clade, except the cambium stem cell regulator WOX4, can substitute for WUS function in shoot and floral stem cell maintenance to different degrees. Stem cell function of WUS requires a canonical WUS-box, essential for interaction with TPL/TPR co-repressors, whereas the repressive EAR domain is dispensable and the acidic domain seems only to be required for female fertility. In contrast to the WUS clade, members of the ancient WOX13 and the WOX9 clades cannot support stem cell maintenance. Although the homeodomains are interchangeable between WUS and WOX9 clade members, a WUS-compatible homeodomain together with canonical WUS-box is not sufficient for stem cell maintenance. Our results suggest that WOX function in shoot and floral meristems of Arabidopsis is restricted to the modern WUS clade, suggesting that stem cell control is a derived function. Yet undiscovered functional domains in addition to the homeodomain and the WUS-box are necessary for this function