Large elastic artery stiffness is an independent predictor of age-related cardiovascular events that is attributable to structural remodeling throughout the artery. The intima, media and adventitial layers of the artery uniquely remodel with advancing age and all contribute to arterial stiffening. The specific expression of the extracellular matrix proteins collagen and elastin, and post-translational modifications of these proteins by advanced glycation end-products are key mechanisms in arterial stiffening with age and will be reviewed in the context of region-specific expression. In addition, interventions for attenuating age-related arterial stiffness and novel imaging advances for translating basic findings to older clinical populations will be discussed.

We report a 61-year-old man presenting with rapidly progressive stiffness and painful muscle spasms in the lower extremity muscles. The patient was diagnosed with chronic lymphocytic leukaemia (CLL) approximately a year before symptom onset. Electromyography displayed continuous motor unit activity and immunocytochemistry showed a positive staining for antiglycine receptor (anti-GlyR) antibodies. The clinical course was complicated by autonomic instability and cardiac arrest, but stabilised under continuous therapy with plasma exchange and symptomatic treatment with baclofen and clonazepam. Anti-GlyR antibodies induce rare, but severe, variants of stiff person syndrome that can be of paraneoplastic origin and life threatening due to autonomic dysfunction.

Heterotopic ossification (HO) is a pathologic condition that leads to the development of bone within nonosseous soft tissues. A common site for HO development is at the hip. The bone that forms is believed to develop through stimulation by cellular mediators and altered neurovascular signaling. Heterotopic ossification can be a debilitating disease leading to pain, edema, and stiffness. This only compounds already-debilitating comorbid conditions such as a spinal cord injury, head injury, or trauma. Several factors, including prostaglandin E2, bone morphogenetic protein, and the inflammatory process, are believed to contribute to the development of HO. The full scope of pathophysiology contributing to HO is not fully understood.

Posterior lumbar structures are vital for spinal stability, and many researchers thought that laminectomy and facetectomy would lead to severe spinal instability. However, because living organisms have compensatory repair capacities, their long-term condition after injuries may change over time. To study the changes in the lumbar biomechanical stability of flexion/extension and torsion at different time points after the resection of various posterior structures, as well as to assess the capacity for self-healing, sheep that had undergone laminectomy or facetectomy were used as an experimental animal model. The injured sheep models included three groups: laminectomy only, laminectomy plus left total facetectomy, and laminectomy plus bilateral facetectomy. Eight nonoperative sheep were used as the control group. At 0, 6, 12, 24, and 36 weeks after injury, the lumbar specimens were harvested for biomechanical testing using the Instron 8874 servohydraulic biomechanical testing system. The changes in the injured lumbar spine were also analyzed through radiological examination. The lumbar stability in flexion/extension and torsion was severely decreased after the three types of surgery. After 6 weeks, the flexion/extension mechanical parameters recovered substantially; each parameter had returned to normal levels by 12 weeks and exceeded the intact group by 24 and 36 weeks. Torsional stiffness also recovered gradually over time. All injury groups demonstrated decreased intervertebral space and degeneration or even fusion in the small joints of the surgical segment or in adjacent segments. These results indicate that the body has the ability to repair the mechanical instability to a certain extent.

Few studies have shown comparison data between calcaneus stiffness index (SI) calculated by quantitative ultrasound (QUS) and bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) in the Chinese population. This study was aimed to examine the correlations between calcaneus SI calculated by QUS and total body BMD and bone mineral content (BMC) measured by DXA in Chinese children and adolescents. We measured the total body BMD and BMC using Lunar Prodigy (GE Healthcare), and speed of sound (SOS), broadband ultrasound attenuation (BUA), and a calculated SI of the left os calcis using Lunar Achilles Express (GE Healthcare) in 392 healthy Chinese schoolchildren and adolescents aged 5-19 years. The short-term precision for DXA was 0.5 % for total body BMD. The precision for QUS was 1.8 % for SI, 2.9 % for BUA, and 0.4 % for SOS. Pearson's correlation coefficients (r) were calculated to assess the possible correlations between the total body BMC by DXA and SI calculated by QUS. There were significantly positive correlations between SI of the left os calcis and total body BMD (r = 0.693, p < 0.001, n = 392) and BMC (r = 0.690, p < 0.001, n = 392). For all the subjects, significant positive correlations were observed between the calcaneal SI and the age, weight, height, BMI, total body BMD, total body BMC, total body lean mass, and total body fat mass, with r ranging from 0.310 (total body fat mass) to 0.693 (total body BMD) (p < 0.001, n = 392). In conclusion, QUS bone densitometry is a useful measuring method showing the physiological bone development in childhood and adolescence.

The onset of neurodegenerative disorders is characterized by the progressive dysfunction and loss of subpopulations of specialized cells within specific regions of the central nervous system (CNS). Since CNS has a limited ability for self-repair and regeneration under such conditions, clinical transplantation of stem cells has been explored as an alternative. Although embryonic stem cells (ESCs) offer a promising therapeutic platform to treat a variety of neurodegenerative disorders, the niche microenvironment, which could regulate their differentiation into specialized lineages on demand, needs to be optimized for successful clinical transplantation. Here, we evaluated the synergistic role of matrix microenvironment (type, architecture, composition, stiffness) and signaling molecules (type, dosage) on murine ESC differentiation into specific neural and glial lineages. ESCs were cultured as embryoid bodies on either 2D substrates or within 3D scaffolds, in the presence or absence of retinoic acid (RA) and sonic hedgehog (Shh). Results showed that ESCs maintained their stemness even after 4 days in the absence of exogenous signaling molecules, as evidenced by Oct-4 staining. RA at 1 μm dosage was deemed optimal for neural differentiation and neurite outgrowth on collagen-1 coated substrates. Significant neural differentiation with robust neurite outgrowth and branching was evident only on collagen-1 coated 2D substrates and within 3D matrigel scaffolds, in the presence of 1 μm RA. Blocking α6 or β1 integrin subunits on differentiating cells inhibited matrigel-induced effects on neural differentiation and neurite outgrowth. Hydrogel concentration strongly regulated formation of neural and astrocyte lineages in 1 μm RA additive cultures. When RA and Shh were provided, either alone or together, 3D collagen-1 scaffolds enhanced significant motor neuron formation, while 3D matrigel stimulated dopaminergic neuron differentiation. These results suggest a synergistic role of microenvironmental cues for ESC differentiation and maturation, with potential applications in cell transplantation therapy.

Total hip replacement (THR) is most often performed to treat end-stage symptomatic osteoarthritis. Patients typically present with increasing pain, restricted mobility and stiffness. In this procedure, the femoral head and part of the femoral neck are excised. The acetabulum is enlarged and an acetabular cup is inserted. The femoral head is replaced by a femoral component, the stem of which is inserted into the medullary canal of the femur. The components can be either cemented in place or press-fit (cementless). The THR concept was popularised by Sir John Charnley in the 1960s and although, over half a century of development has resulted in incremental improvements, the procedure is not dramatically different from the one he described. However, over the last two decades there have been significant changes in the types of bearing surfaces used. Metal on polyethylene continues to be the workhorse for the majority of cases. In the young and active, bearing surfaces with low wear rate are increasingly used. Since the early 1960s, THR has played an important role in alleviating pain and restoring mobility to millions of people. The cost-effectiveness of THR in treating advanced osteoarthritis makes it one of the most successful of all surgical interventions.

CONTEXT:

Mechanical properties are essential for biological functions of the hyaline cartilage such as energy dissipation and diffusion of solutes. Mechanical properties are primarily dependent on the hierarchical organization of the two major extracellular matrix (ECM) macromolecular components of the cartilage: the fibrillar collagen network and the glycosaminoglycan (GAG)-substituted proteoglycan, mainly aggrecan, aggregates. Interaction of chondrocytes, the only cell type in the tissue, with the ECM through adhesion receptors is involved in establishing mechanical stability via bidirectional transduction of both mechanical forces and chemical signals. In this study, we aimed to determine the role of the transmembrane β1 integrin adhesion receptors in cartilage biomechanical properties by the use of genetic modification in mice.

METHODS:

Costal cartilages of wild type and mutant mice lacking β1 integrins in chondrocytes were investigated. Cartilage compressive properties and solute diffusion were characterized by rheometric analysis and Fluorescence Recovery After Photobleaching (FRAP), respectively. Cartilage tissue sections were analyzed by histology, immunohistochemistry and transmission electron microscopy (TEM).

RESULTS:

At the histological level, the mutant costal cartilage was characterized by chondrocyte rounding and loss of tissue polarity. Immunohistochemistry and safranin orange staining demonstrated apparently normal aggrecan and GAG levels, respectively. Antibody staining for collagen II and TEM showed comparable expression and organization of the collagen fibrils between mutant and control cartilages. Despite the lack of gross histological and ultrastructural abnormalities, rheological measurements revealed that the peak elastic modulus in compression of mutant cartilage was 1.6-fold higher than the peak elastic modulus of wild-type sample. Interestingly, the diffusion coefficient within the mutant cartilage tissue was found to be 1.2-fold lower in the extracellular space and 14-fold lower in the pericellular (PCM) space compared to control.

CONCLUSION:

The results demonstrate that the absence of β1 integrins on the surface of chondrocytes increases the stiffness and modifies the diffusion properties of costal cartilage. Our data imply that β1 integrins-mediated chondrocyte-matrix interactions directly affect cartilage biomechanics probably by modifying physical properties of individual cells. This study thus highlights the crucial role of β1 integrins in the cartilage function.

BACKGROUND:

In patients with severe aortic stenosis, left ventricular hypertrophy is associated with increased myocardial stiffness and dysfunction linked to cardiac morbidity and mortality. We aimed at systematically investigating the degree of left ventricular mass regression and changes in left ventricular function six months after transcatheter aortic valve implantation (TAVI) by cardiovascular magnetic resonance (CMR).

METHODS:

Left ventricular mass indexed to body surface area (LVMi), end diastolic volume indexed to body surface area (LVEDVi), left ventricular ejection fraction (LVEF) and stroke volume (SV) were investigated by CMR before and six months after TAVI in patients with severe aortic stenosis and contraindications for surgical aortic valve replacement.

RESULTS:

Twenty-sevent patients had paired CMR at baseline and at 6-month follow-up (N=27), with a mean age of 80.7+/-5.2 years. LVMi decreased from 84.5+/-25.2 g/m2 at baseline to 69.4+/-18.4 g/m2 at six months follow-up (P<0.001). LVEDVi (87.2+/-30.1 ml /m2vs 86.4+/-22.3 ml/m2; P=0.84), LVEF (61.5+/-14.5% vs 65.1+/-7.2%, P=0.08) and SV (89.2+/-22 ml vs 94.7+/-26.5 ml; P=0.25) did not change significantly.

CONCLUSIONS:

Based on CMR, significant left ventricular reverse remodeling occurs six months after TAVI.

Arterial stiffening is a widely known physiological change that occurs with ageing, but the functional consequences of vascular ageing are unclear. The purpose of this study was to determine whether carotid-femoral pulse wave velocity (PWV), mechanical properties of the carotid and femoral arteries and/or peripheral perfusion was associated with gait performance measured using a 400-m walk test. Twenty-one healthy older (68 ± 5 years) adults without cardiovascular disease participated in this study. Applanation tonometry was used to measure PWV, and Doppler ultrasound was used to measure arterial wall properties of the left common carotid and common femoral artery along with femoral blood flow. The median walk distance in the first 2 min of the test was 585 ft, and the overall gait speed was 1·5 m s(-1) . Gait performance was inversely correlated with PWV (distance: r = -0·51; speed: r = -0·48; P<0·05) and carotid artery stiffness index β (distance: r = -0·56; speed: r = -0·51; P<0·05) after adjustment for age, body mass index, waist circumference and systolic blood pressure. No significant correlations were found between gait performance and femoral artery stiffness index β or femoral artery blood flow. These results found higher central arterial stiffness, as assessed by segmental arterial stiffness or local arterial wall properties, is associated with lower gait performance in older adults independent of other confounders.