Mechanical and Structural Properties of Articular Cartilage and Subchondral Bone in Human Osteoarthritic Knees.

Knee osteoarthritis (OA), characterized by multiple joint tissue degenerations, remains a significant clinical challenge. Recent evidence suggests that crosstalk within the osteochondral unit may drive OA progression. While structural-biomechanical properties of bone and cartilage have been studied, potential interaction within the osteochondral unit in the context of OA has yet to be investigated. We performed comprehensive structural and biomechanical quantification of the cartilage, subchondral bone plate, and subchondral trabecular bone using 101 osteochondral cores collected from tibial plateaus of 12 control human cadavers (CT, 5 male/7 female) and 19 patients undergoing total knee replacement (OA, 6 male/13 female). For each sample, we quantified subchondral bone plate microstructure, plate-and-rod morphological properties of the subchondral trabecular bone using individual trabecula segmentation, and morphological and compositional properties of the articular cartilage. We also performed indentation testing on each compartment of the osteochondral unit to extract the respective structural-mechanical properties. Cartilage thickness was lower in moderate and severe OA regions, while OARSI score was higher only in severe OA regions. GAG content did not change in any OA region. Aggregate and shear moduli were lower only in severe OA regions, while permeability was lower only in moderate OA regions. In the subchondral bone plate, thickness and TMD were higher in moderate and severe OA regions. Tissue modulus of subchondral trabecular bone was lower in moderate OA regions despite a thicker and more mineralized subchondral bone plate; this deterioration was not observed in severe OA regions. Regression analysis revealed strong correlations between cartilage and subchondral trabecular bone properties in CT; these correlations were also found in moderate OA regions but were not observed in severe OA regions. In summary, our findings comprehensively characterize the human OA osteochondral unit. Importantly, uncoupling cartilage and subchondral bone structural-mechanical properties may be a hallmark of OA.

Knee osteoarthritis (OA) is a complex condition involving the degradation of joint tissues. To better understand OA progression, we investigated the interplay between different components of the joint. Our study focused on how cartilage, subchondral bone plate, and subchondral trabecular bone interact in human knee OA samples. We observed distinct changes in these tissues in moderate and severe OA regions compared to healthy joints. In moderate to severe OA, we found that cartilage thickness decreased while the subchondral bone plate thickened. Interestingly, the strength of the subchondral trabecular bone decreased only in moderate OA regions, not in severe OA. Moreover, our analysis revealed strong correlations between cartilage and subchondral trabecular bone properties in healthy joints and moderate OA regions. However, these correlations were absent in severe OA regions, indicating a disruption in the usual relationship between these tissues. Overall, our findings shed light on the structural and biomechanical changes occurring within the knee joint in OA. Understanding these changes may offer insights into potential therapeutic strategies for managing OA.

Association between serum galectin-3 and chronic obstructive pulmonary disease: A meta-analysis.

Chronic obstructive pulmonary disease (COPD) is a significant public health issue characterized by progressive and irreversible airflow limitation. The aim of this meta-analysis was to determine the association between changes in serum galectin-3 levels and COPD and to assess the relationship between serum galectin-3 levels and acute exacerbations of COPD (AECOPD). Relevant observational studies were retrieved from electronic databases, including PubMed, Web of Science, Embase, Wanfang, and China National Knowledge Infrastructure (CNKI). A random-effects model was used to combine the data, incorporating the influence of between-study heterogeneity. Twelve case-control studies were included. The pooled results showed a significantly higher serum level of galectin-3 in patients with COPD compared to controls (standardized mean difference [SMD] 0.60; 95% confidence interval [CI] 0.40 - 0.80; P < 0.001; I2 = 68%). Further meta-analysis suggested higher levels of serum galectin-3 in patients with AECOPD compared to those with stable COPD (SMD 0.33; 95% CI 0.20 - 0.46; P < 0.001; I2 = 0%). Subgroup analyses according to the mean age of the participants, the proportion of males, and study quality scores did not significantly change the results (P for subgroup differences all > 0.05). In conclusion, patients with COPD were found to have higher serum levels of galectin-3, with levels further elevated in patients with AECOPD compared to those with stable COPD.

Individual trabecula segmentation validation in first- and second-generation high-resolution peripheral computed tomography compared to micro-computed tomography in the distal radius and tibia.

High-resolution peripheral quantitative computed tomography (HR-pQCT) has been used for in vivo 3D visualization of trabecular microstructure. Second-generation HR-pQCT (HR-pQCT II) has been shown to have good agreement with first generation HR-pQCT (HR-pQCT I). Advanced Individual Trabecula Segmentation (ITS) decomposes the trabecula network into individual plates and rods. ITS based on HR-pQCT I showed a strong correlation to ITS based on micro-computed tomography (µCT) and identified trabecular changes in metabolic bone diseases. ITS based on HR-pQCT II has new potential because of the enhanced resolution but has yet to be validated. The objective of this study was to assess the agreement between ITS based on HR-pQCT I, HR-pQCT II, and µCT to assess the capability of ITS on HR-pQCT images as a tool for studying bone structure. Freshly frozen tibia and radius bones were scanned in the distal region using HR-pQCT I at 82 µm, HR-pQCT II at 60.7 µm, and µCT at 37 µm. Images were registered, binarized, and ITS analysis was performed. Bone volume fraction (pBV/TV, rBV/TV), number density (pTb.N, rTb.N), thickness (pTb.Th, rTb.Th), and plate-to-rod (PR) ratio (pBV/rBV) of trabecular plates and rods were obtained. Paired Student's t-tests with post hoc Bonferroni analysis were used to examine the differences. Linear regression was used to determine the correlation coefficient. The HR-pQCT I parameters were different from the µCT measurements. The HR-pQCT II parameters were different from the µCT measurements except for rTb.N, and the HR-pQCT I parameters were different from the HR-pQCT II measurements except for pTb.Th. The strong correlation between HR-pQCT II and µCT microstructural analysis (R2 = 0.55-0.94) suggests that HR-pQCT II can be used to assess changes in plate and rod microstructure and that values from HR-pQCT I can be corrected.

Amygdalin Improves Allergic Asthma via the Thymic Stromal Lymphopoietin-dendritic Cell-OX40 Ligand Axis in a Mouse Model.

Asthma, characterized by persistent inflammation and increased sensitivity of the airway, is the most common chronic condition among children. Novel, safe, and reliable treatment strategies are the focus of current research on pediatric asthma. Amygdalin, mainly present in bitter almonds, has anti-inflammatory and immunoregulatory potential, but its effect on asthma remains uninvestigated. Here, the impact of amygdalin on the thymic stromal lymphopoietin (TSLP)-dendritic cell (DC)-OX40L axis was investigated. A BALB/c mouse model for allergic asthma was established using the ovalbumin-sensitization method. Amygdalin treatment was administered between days 21 and 27 of the protocol. Cell numbers and hematoxylin and eosin (H&E) staining in bronchoalveolar lavage fluid (BALF) were used to observe the impact of amygdalin on airway inflammation. TSLP, IL-4, IL-5, IL-13, and IFN-γ concentrations were determined via Enzyme-linked immunosorbent assay (ELISA). TSLP, GATA-3, and T-bet proteins were measured using western blotting. Cell-surface receptor expression on DCs (MHC II, CD80, and CD86) was assessed via flow cytometry. OX40L mRNA and protein levels were detected using western blotting and qRT-PCR, respectively. Amygdalin treatment attenuated airway inflammation decreased BALF TSLP levels, inhibited DC maturation, restrained TSLP-induced DC surface marker expression (MHCII, CD80, and CD86), and further decreased OX40L levels in activated DCs. This occurred together with decreased Th2 cytokine levels (IL-4, IL-5, and IL-13) and GATA3 expression, whereas Th1 cytokine (IFN-γ) levels and T-bet expression increased. Amygdalin thus regulates the Th1/Th2 balance through the TSLP-DC-OX40L axis to participate in inflammation development in the airways, providing a basis for potential allergic asthma treatments.

Anti-Siglec-15 Antibody Prevents Marked Bone Loss after Acute Spinal Cord Injury-Induced Immobilization in Rats.

Rapid and extensive sublesional bone loss after spinal cord injury (SCI) is a difficult medical problem that has been refractory to available interventions except the antiresorptive agent denosumab (DMAB). While DMAB has shown some efficacy in inhibiting bone loss, its concurrent inhibition of bone formation limits its use. Sialic acid-binding immunoglobulin-like lectin (Siglec)-15 is expressed on the cell surface of mature osteoclasts. Anti-Siglec-15 antibody (Ab) has been shown to inhibit osteoclast maturation and bone resorption while maintaining osteoblast activity, which is distinct from current antiresorptive agents that inhibit the activity of both osteoclasts and osteoblasts. The goal of the present study is to test a Siglec-15 Ab (NP159) as a new treatment option to prevent bone loss in an acute SCI model. To this end, 4-month-old male Wistar rats underwent complete spinal cord transection and were treated with either vehicle or NP159 at 20 mg/kg once every 2 weeks for 8 weeks. SCI results in significant decreases in bone mineral density (BMD, -18.7%), trabecular bone volume (-43.1%), trabecular connectivity (-59.7%), and bone stiffness (-76.3%) at the distal femur. Treatment with NP159 almost completely prevents the aforementioned deterioration of bone after SCI. Blood and histomorphometric analyses revealed that NP159 is able to greatly inhibit bone resorption while maintaining bone formation after acute SCI. In ex vivo cultures of bone marrow cells, NP159 reduces osteoclastogenesis while increasing osteoblastogenesis. In summary, treatment with NP159 almost fully prevents sublesional loss of BMD and metaphysis trabecular bone volume and preserves bone strength in a rat model of acute SCI. Because of its unique ability to reduce osteoclastogenesis and bone resorption while promoting osteoblastogenesis to maintain bone formation, Siglec-15 Ab may hold greater promise as a therapeutic agent, compared with the exclusively antiresorptive or anabolic agents that are currently used, in mitigating the striking bone loss that occurs after SCI or other conditions associated with severe immobilization. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Yap controls notochord formation and neural tube patterning by integrating mechanotransduction with FoxA2 and Shh expression.

Correct notochord and neural tube (NT) formation is crucial to the development of the central nervous system and midline structures. Integrated biochemical and biophysical signaling controls embryonic growth and patterning; however, the underlying mechanisms remain poorly understood. Here, we took the opportunities of marked morphological changes during notochord and NT formation and identified both necessary and sufficient roles of Yap, a key mechanosensor and mechanotransducer, in biochemical signaling activation during formation of notochord and floor plate, the ventral signaling centers that pattern the dorsal-ventral axis of NT and the surrounding tissues. We showed that Yap activation by a gradient of mechanical stress and tissue stiffness in the notochord and ventral NT induces FoxA2 and Shh expression. Hedgehog signaling activation rescued NT patterning defects caused by Yap deficiency, but not notochord formation. Therefore, mechanotransduction via Yap activation acts in feedforward mechanisms to induce FoxA2 expression for notochord formation and activate Shh expression for floor plate induction by synergistically interacting with FoxA2.

Early zoledronate treatment inhibits subchondral bone microstructural changes in skeletally-mature, ACL-transected canine knees.

Anterior cruciate ligament (ACL) tear leads to post-traumatic osteoarthritis (PTOA), a significant clinical burden worldwide that currently has no cure. Recent studies suggest a role of subchondral bone adaptations in the development of PTOA. Particularly, microstructural changes in the rod-and-plate microstructure of subchondral bone may precede and contribute to OA progression. In this study, we quantified microstructural changes in subchondral trabecular rods and plates after ACL-transection for the first time in the well-established preclinical canine model of PTOA and investigated the therapeutic potentials of a bisphosphonate (zoledronate) and NSAID treatment (meloxicam). Unilateral hindlimb ACL transection was performed on skeletally-mature (2-year-old, N = 20) and juvenile (10-month-old, N = 20) male beagles. Animals were assigned to 4 groups (N = 5): ACLT, un-operated control, ACLT with zoledronate, and ACLT with meloxicam treatment. Subchondral bone microstructure was evaluated by micro-computed tomography and cartilage integrity was evaluated histologically. We found that ACL-induced subchondral bone changes depended on skeletal maturity of animals. In mature animals, significant loss of trabecular plates that resulted in reduced PR ratio occurred at Month 1 and persisted until Month 8. Zoledronate treatment prevented trabecular plate loss while meloxicam treatment did not. Whether cartilage degeneration is also attenuated warrants further investigation. In juvenile animals that have not reached skeletal maturity, transient changes in trabecular plate and rod microstructure occurred at Month 3 but not Month 9. Neither zoledronate nor meloxicam treatment attenuated bone microstructural changes or cartilage damages. Findings from this study suggest that early inhibition of bone resorption by bisphosphonate after injury may be a promising therapeutic approach to prevent alterations in subchondral bone microstructure associated with PTOA. Our results further demonstrate that pathogenesis of PTOA may differ between adolescent and adult patients and therefore require distinct management strategies.

Spine Volumetric BMD and Strength in Premenopausal Idiopathic Osteoporosis: Effect of Teriparatide Followed by Denosumab.

CONTEXT: Premenopausal women with idiopathic osteoporosis (PreMenIOP) have marked deficits in bone density, microstructure, and strength. OBJECTIVE: To define effects of treatment with teriparatide followed by denosumab on lumbar spine (LS) volumetric bone mineral density (vBMD) and stiffness by finite element analysis assessed on central quantitative computed tomography (cQCT) scans. DESIGN, SETTINGS, AND PARTICIPANTS: Ancillary analysis of baseline, post-teriparatide, and post-denosumab cQCT scans from a randomized trial of 41 women allocated to teriparatide (20 mcg daily; n = 28) or placebo (n = 11). After 6 months, those on teriparatide continued for 18 months, and those on placebo switched to teriparatide for 24 months. After completing teriparatide, 33 enrolled in a Phase 2B extension with denosumab (60 mg every 6 months) for 12 months. MAIN OUTCOME MEASURES: Primary outcomes were percentage change from baseline in LS trabecular vBMD and stiffness after teriparatide and between end of teriparatide and completing denosumab. Percentage change from baseline in LS trabecular vBMD and stiffness after sequential teriparatide and denosumab were secondary outcomes. FINDINGS: There were large increases (all Ps < 0.001) in trabecular vBMD (25%), other vBMD parameters, and stiffness (21%) after teriparatide. Statistically significant increases in trabecular vBMD (10%; P < 0.001) and other vBMD parameters (P = 0.03-0.001) were seen after denosumab, while stiffness increased by 7% (P = 0.068). Sequential teriparatide and denosumab led to highly significant (all Ps < 0.001) increases LS trabecular vBMD (43%), other vBMD parameters (15-31%), and stiffness (21%). CONCLUSIONS: The large and statistically significant increases in volumetric density and stiffness after sequential treatment with teriparatide followed by denosumab are encouraging and support use of this regimen in PreMenIOP.

The effect of denosumab and alendronate on trabecular plate and rod microstructure at the distal tibia and radius: A post-hoc HR-pQCT study.

BACKGROUND: Age-related trabecular microstructural deterioration and conversion from plate-like trabeculae to rod-like trabeculae occur because of unbalanced rapid remodeling. As denosumab achieves greater remodeling suppression and lower cortical porosity than alendronate, we hypothesized that denosumab might also preserve trabecular plate microstructure, bone stiffness and strength more effectively than alendronate. METHODS: In this post hoc analysis of a phase 2 study, postmenopausal women randomized to placebo (P, n = 74), denosumab (D, n = 72), or alendronate (A, n = 68). HR-pQCT scans of the distal radius and tibia were performed at baseline and Month-12 (M12). Trabecular compartment was subjected to Individual Trabecula Segmentation while finite element analysis was performed to estimate stiffness and strength. Percent change from baseline at M12 of each parameter was compared between patient groups. RESULTS: At the distal tibia, in the placebo group, plate surface area (pTb.S, -1.3%) decreased while rod bone volume fraction (rBV/TV, +4.5%) and number (rTb.N, +2.1%) increased. These changes were prevented by denosumab but persisted despite alendronate therapy (pTb.S: -1.7%; rBV/TV: +6.9%; rTb.N: +3.0%). Both treatments improved whole bone stiffness (D: +3.1%; A: +1.8%) and failure load (D: +3.0%; A: +2.2%); improvements using denosumab was significant compared to placebo (stiffness: p = 0.004; failure load: p = 0.003). At the distal radius, denosumab increased total trabecular bone volume fraction (BV/TV, +3.4%) and whole bone failure load (+4.0%), significantly different from placebo (BV/TV: p = 0.044; failure load: p = 0.046). Significantly different effects of either drug on plate and rod microstructure were not detected. CONCLUSIONS: Denosumab preserved trabecular plate microstructure. Alendronate did not. However, estimated strength did not differ between denosumab and alendronate treated groups.

Transient neonatal shoulder paralysis causes early osteoarthritis in a mouse model.

Neonatal brachial plexus palsy (NBPP) occurs in approximately 1.5 of every 1,000 live births. The majority of children with NBPP recover function of the shoulder. However, the long-term risk of osteoarthritis (OA) in this population is unknown. The purpose of this study was to investigate the development of OA in a mouse model of transient neonatal shoulder paralysis. Neonatal mice were injected twice per week for 4 weeks with saline in the right supraspinatus muscle (Saline, control) and botulinum toxin A (BtxA, transient paralysis) in the left supraspinatus muscle, and then allowed to recover for 20 or 36 weeks. Control mice received no injections, and all mice were sacrificed at 24 or 40 weeks. BtxA mice exhibited abnormalities in gait compared to controls through 10 weeks of age, but these differences did not persist into adulthood. BtxA shoulders had decreased bone volume (-9%) and abnormal trabecular microstructure compared to controls. Histomorphometry analysis demonstrated that BtxA shoulders had higher murine shoulder arthritis scale scores (+30%), and therefore more shoulder OA compared to controls. Articular cartilage of BtxA shoulders demonstrated stiffening of the tissue. Compared with controls, articular cartilage from BtxA shoulders had 2-fold and 10-fold decreases in Dkk1 and BMP2 expression, respectively, and 3-fold and 14-fold increases in Col10A1 and BGLAP expression, respectively, consistent with established models of OA. In summary, a brief period of paralysis of the neonatal mouse shoulder was sufficient to generate early signs of OA in adult cartilage and bone.

Toughening mechanisms for the attachment of architectured materials: The mechanics of the tendon enthesis.

Architectured materials offer tailored mechanical properties but are limited in engineering applications due to challenges in maintaining toughness across their attachments. The enthesis connects tendon and bone, two vastly different architectured materials, and exhibits toughness across a wide range of loadings. Understanding the mechanisms by which this is achieved could inform the development of engineered attachments. Integrating experiments, simulations, and previously unexplored imaging that enabled simultaneous observation of mineralized and unmineralized tissues, we identified putative mechanisms of enthesis toughening in a mouse model and then manipulated these mechanisms via in vivo control of mineralization and architecture. Imaging uncovered a fibrous architecture within the enthesis that controls trade-offs between strength and toughness. In vivo models of pathology revealed architectural adaptations that optimize these trade-offs through cross-scale mechanisms including nanoscale protein denaturation, milliscale load-sharing, and macroscale energy absorption. Results suggest strategies for optimizing architecture for tough bimaterial attachments in medicine and engineering.

Microstructure Determines Apparent-Level Mechanics Despite Tissue-Level Anisotropy and Heterogeneity of Individual Plates and Rods in Normal Human Trabecular Bone.

Trabecular plates and rods determine apparent elastic modulus and yield strength of trabecular bone, serving as important indicators of bone's mechanical integrity in health and disease. Although trabecular bone's apparent-level mechanical properties have been widely reported, tissue mechanical properties of individual trabeculae have not been fully characterized. We systematically measured tissue mineral density (TMD)-dependent elastic modulus of individual trabeculae using microindentation and characterized its anisotropy as a function of trabecular type (plate or rod), trabecular orientation in the global coordinate (longitudinal, oblique, or transverse along the anatomic loading axis), and indentation direction along the local trabecular coordinate (axial or lateral). Human trabecular bone samples were scanned by micro-computed tomography for TMD and microstructural measurements. Individual trabecula segmentation was used to decompose trabecular network into individual trabeculae, where trabecular type and orientation were determined. We performed precise, selective indentation of trabeculae in each category using a custom-built, microscope-coupled microindentation device. Co-localization of TMD at each indentation site was performed to obtain TMD-to-modulus correlations. We found significantly higher TMD and tissue modulus in trabecular plates than rods. Regardless of trabecular type and orientation, axial tissue modulus was consistently higher than lateral tissue modulus, with ratios ranging from 1.13 to 1.41. Correlations between TMD and tissue modulus measured from axial and lateral indentations were strong but distinct: axial correlation predicted higher tissue modulus than lateral correlation at the same TMD level. To assess the contribution of experimentally measured anisotropic tissue properties of individual trabeculae to apparent-level mechanics, we constructed non-linear micro-finite element models using a new set of trabecular bone samples and compared model predictions to mechanical testing measurements. Heterogeneous anisotropic models accurately predicted apparent elastic modulus but were no better than a simple homogeneous isotropic model. Variances in tissue-level properties may therefore contribute nominally to apparent-level mechanics in normal human trabecular bone. © 2021 American Society for Bone and Mineral Research (ASBMR).

Mechanical stress determines the configuration of TGFß activation in articular cartilage.

Our incomplete understanding of osteoarthritis (OA) pathogenesis has significantly hindered the development of disease-modifying therapy. The functional relationship between subchondral bone (SB) and articular cartilage (AC) is unclear. Here, we found that the changes of SB architecture altered the distribution of mechanical stress on AC. Importantly, the latter is well aligned with the pattern of transforming growth factor beta (TGFß) activity in AC, which is essential in the regulation of AC homeostasis. Specifically, TGFß activity is concentrated in the areas of AC with high mechanical stress. A high level of TGFß disrupts the cartilage homeostasis and impairs the metabolic activity of chondrocytes. Mechanical stress stimulates talin-centered cytoskeletal reorganization and the consequent increase of cell contractile forces and cell stiffness of chondrocytes, which triggers αV integrin-mediated TGFß activation. Knockout of αV integrin in chondrocytes reversed the alteration of TGFß activation and subsequent metabolic abnormalities in AC and attenuated cartilage degeneration in an OA mouse model. Thus, SB structure determines the patterns of mechanical stress and the configuration of TGFß activation in AC, which subsequently regulates chondrocyte metabolism and AC homeostasis.

Electrical stimulation of hindlimb skeletal muscle has beneficial effects on sublesional bone in a rat model of spinal cord injury.

Spinal cord injury (SCI) results in marked atrophy of sublesional skeletal muscle and substantial loss of bone. In this study, the effects of prolonged electrical stimulation (ES) and/or testosterone enanthate (TE) on muscle mass and bone formation in a rat model of SCI were tested. Compared to sham-transected animals, a significant reduction of the mass of soleus, plantaris and extensor digitorum longus (EDL) muscles was observed in animals 6 weeks post-SCI. Notably, ES or ES + TE resulted in the increased mass of the EDL muscles. ES or ES + TE significantly decreased mRNA levels of muscle atrophy markers (e.g., MAFbx and MurF1) in the EDL. Significant decreases in bone mineral density (BMD) (-27%) and trabecular bone volume (-49.3%) at the distal femur were observed in animals 6 weeks post injury. TE, ES and ES + TE treatment significantly increased BMD by +6.4%, +5.4%, +8.5% and bone volume by +22.2%, and +56.2% and+ 60.2%, respectively. Notably, ES alone or ES + TE resulted in almost complete restoration of cortical stiffness estimated by finite element analysis in SCI animals. Osteoblastogenesis was evaluated by colony-forming unit-fibroblastic (CFU-F) staining using bone marrow mesenchymal stem cells obtained from the femur. SCI decreased the CFU-F+ cells by -56.8% compared to sham animals. TE or ES + TE treatment after SCI increased osteoblastogenesis by +74.6% and +67.2%, respectively. An osteoclastogenesis assay revealed significantly increased TRAP+ multinucleated cells (+34.8%) in SCI animals compared to sham animals. TE, ES and TE + ES treatment following SCI markedly decreased TRAP+ cells by -51.3%, -40.3% and -46.9%, respectively. Each intervention greatly reduced the ratio of RANKL to OPG mRNA of sublesional long bone. Collectively, our findings demonstrate that after neurologically complete paralysis, dynamic muscle resistance exercise by ES reduced muscle atrophy, downregulated genes involved in muscle wasting, and restored mechanical loading to sublesional bone to a degree that allowed for the preservation of bone by inhibition of bone resorption and/or by facilitating bone formation.

Administration of High-Dose Methylprednisolone Worsens Bone Loss after Acute Spinal Cord Injury in Rats.

The administration of high-dose methylprednisolone (MP) for 24-48 h after traumatic spinal cord injury (SCI) has been shown to improve functional recovery. The known adverse effects of MP on skeletal muscle and the immune system, though, have raised clinically relevant safety concerns. However, the effect of MP administration on SCI-induced bone loss has not been evaluated to date. This study examined the adverse effects of high-dose MP administration on skeletal bone after acute SCI in rodents. Male rats underwent spinal cord transection at T3-T4, which was followed by an intravenous injection of MP and subsequent infusion of MP for 24 h. At 2 days, animals were euthanized and hindlimb bone samples were collected. MP significantly reduced bone mineral density (-6.7%) and induced deterioration of bone microstructure (trabecular bone volume/tissue volume, -18.4%; trabecular number, -19.4%) in the distal femur of SCI rats. MP significantly increased expression in the hindlimb bones of osteoclastic genes receptor activator of nuclear factor-κB ligand (RANKL; +402%), triiodothyronine receptor auxiliary protein (+32%), calcitonin receptor (+41%), and reduced osteoprotegerin/RANKL ratio (-72%) compared to those of SCI-vehicle animals. Collectively, 1 day of high-dose MP at a dose comparable to the dosing regimen prescribed to patients who qualify to receive this treatment approach with acute SCI increased loss of bone mass and integrity below the level of lesion than that of animals that had SCI alone, and was associated with further elevation in the expression of genes involved in pathways associated with osteoclastic bone resorption than that observed in SCI animals.

Long-term Bone Loss and Deterioration of Microarchitecture After Gastric Bypass in African American and Latina Women.

CONTEXT: The prevalence of obesity is burgeoning among African American and Latina women; however, few studies investigating the skeletal effects of bariatric surgery have focused on these groups. OBJECTIVE: To investigate long-term skeletal changes following Roux-en-Y gastric bypass (RYGB) in African American and Latina women. DESIGN: Four-year prospective cohort study. PATIENTS: African American and Latina women presenting for RYGB (n = 17, mean age 44, body mass index 44 kg/m2) were followed annually for 4 years postoperatively. MAIN OUTCOME MEASURES: Dual-energy x-ray absorptiometry (DXA) measured areal bone mineral density (aBMD) at the spine, hip, and forearm, and body composition. High-resolution peripheral quantitative computed tomography measured volumetric bone mineral density (vBMD) and microarchitecture. Individual trabecula segmentation-based morphological analysis assessed trabecular morphology and connectivity. RESULTS: Baseline DXA Z-Scores were normal. Weight decreased ~30% at Year 1, then stabilized. Parathyroid hormone (PTH) increased by 50% and 25-hydroxyvitamin D was stable. By Year 4, aBMD had declined at all sites, most substantially in the hip. There was significant, progressive loss of cortical and trabecular vBMD, deterioration of microarchitecture, and increased cortical porosity at both the radius and tibia over 4 years. There was loss of trabecular plates, loss of axially aligned trabeculae, and decreased trabecular connectivity. Whole bone stiffness and failure load declined. Risk factors for bone loss included greater weight loss, rise in PTH, and older age. CONCLUSIONS: African American and Latina women had substantial and progressive bone loss, deterioration of microarchitecture, and trabecular morphology following RYGB. Further studies are critical to understand the long-term skeletal consequences of bariatric surgery in this population.

Fabrication of Self-Cleaning Superhydrophobic Surfaces with Improved Corrosion Resistance on 6061 Aluminum Alloys.

Aluminum alloys are widely used, but they are prone to contamination or damage under harsh working environments. In this paper, a self-cleaning superhydrophobic aluminum alloy surface with good corrosion resistance was successfully fabricated via the combination of sand peening and electrochemical oxidation, and it was subsequently covered with a fluoroalkylsilane (FAS) film. The surface morphology, surface wettability, and corrosion resistance were investigated using a scanning electron microscope (SEM), an optical contact angle measurement, and an electrochemical workstation. The results show that binary rough structures and an FAS film with a low surface energy on the Al alloy surfaces confer good superhydrophobicity with a water contact angle of 167.5 ± 1.1° and a sliding angle of 2.5 ± 0.7°. Meanwhile, the potentiodynamic polarization curve shows that the corrosion potential has a positively shifted trend, and the corrosion current density decreases by three orders of magnitude compared with that of the original aluminum alloy sample. In addition, the chemical stability of the as-prepared superhydrophobic surface was evaluated by dripping test using solutions with different pH values for different immersion time. It indicates that the superhydrophobic surface could provide long-term corrosion protection for aluminum alloys. Consequently, the as-prepared superhydrophobic surface has excellent contamination resistance and self-cleaning efficacy, which are important for practical applications.

Experimental Investigation on Ultrasonic Atomization Assisted Turning of Titanium Alloy.

There are high cutting temperatures, large tool wear, and poor tool life in conventional machining, owing to the superior strength and low thermal conductivity of titanium alloy. In this work, ultrasonic atomization assisted turning (UAAT) of Ti6Al4V was performed with a mixed water-soluble oil-based cutting fluid, dispersed into tiny droplets by the high frequency vibration of a piezoelectric crystal. Different cutting speeds and two machining environments, dry and ultrasonic atomization assisted machining, were considered in the investigation of tool life, tool wear morphology, surface roughness, and chip morphology. In comparison with dry machining, UAAT shows lower tool wear and longer tool life due to the advantages of cooling and lubrication. Furthermore, better surface roughness, smoother chip edges, and shorter tool-chip contact length were obtained with UAAT.

Three-dimensional rendering of trabecular bone microarchitecture using a probabilistic approach.

In the past, researchers have attempted to model trabecular bone using computational techniques. However, only a few of these models are visually similar, but not representative of the microstructural characteristics of real trabecular bones. In this study, we hypothesized that probabilistic modeling approaches could be used to generate representative digital models that capture the microstructural features of real trabecular bones. To test this hypothesis, we proposed a novel mathematical framework to build the digital models and compared the digital models to real bone specimens. First, an initial three-dimensional cellular structure was generated using Voronoi tessellation, with the faces and edges of the Voronoi cells considered as a pool of potential trabecular plates and rods, respectively. Then, inverse Monte Carlo simulations were performed to select, delete, or reassign plates and rods until the underlying size, orientation, and spatial distributions of the plates and rods converged to the target distributions obtained from real trabecular bone microstructures. Next, digital graphics techniques were used to define the thickness of trabecular plates and the diameter of trabecular rods, followed by writing the model into a Standard Tessellation Language file and then smoothing the model surfaces for a more natural appearance. To verify the efficacy of the digital model in capturing the microstructural features of real trabecular bones, forty-six digital models with a large variation in microstructural features were generated based on the target distributions obtained from trabecular bone specimens of twelve human cadaveric femurs. Then, the histomorphological parameters of the digital models were compared with those of the real trabecular bone specimens. The results indicate that the digital models are capable of capturing major microstructural features of the trabecular bone samples, thus proving the hypothesis that the proposed probabilistic modeling approach could render real trabecular bone microstructures.

The effects of pubertal exposure to bisphenol-A on social behavior in male mice.

Puberty is a crucial developmental period for structural modifications of brain and activation of the neural circuits underlying sex differences in social behavior. It is possible that pubertal exposure to bisphenol-A (BPA), a common EED with a weak estrogenic activity, influences social behavior. After being exposed to BPA at 0.04, 0.4, 4 mg kg-1 for 18 days, the 7-week-old male mice were tested with social play and three-chamber. The results showed that pubertal BPA exposure decreased social play between adolescent males and sociability of adolescent males. Further, pubertal BPA exposure reduced sociability and inhibited social novel preferences of adult males. BPA inhibited social interactions with opposite sex but improved socio-sexual exploration and the low-intensity mating behavior (mounting) with same sex in adult males. In residential-intruder test, BPA-exposed adult males showed a decrease in aggressiveness and an enhancement in prosocial behavior with intruder. Western blot analysis showed that BPA (especially at 4 mg/kg/d) down-regulated the levels of AR in the amygdala and the striatum but up-regulated the levels of DR1 and DAT proteins in the striatum of adult males. BPA at 4 mg kg-1 decreased the levels of T in the serum and the brain. These results suggest that pubertal BPA exposure affects social play and sociability of adolescent males and even results in long-term effects on social behavior of adult males. BPA-induced down-regulations of the levels of AR in the amygdala and the striatum and up-regulation of the levels of DR1 and DAT in the striatum may be involved.