Compressive and tensile mechanical properties of the porcine nasal septum

The expanding nasal septal cartilage is believed to create a force that powers midfacial growth. In addition, the nasal septum is postulated to act as a mechanical strut that prevents the structural collapse of the face under masticatory loads. Both roles imply that the septum is subject to complex biomechanical loads during growth and mastication. The purpose of this study was to measure the mechanical properties of the nasal septum to determine (1) whether the cartilage is mechanically capable of playing an active role in midfacial growth and in maintaining facial structural integrity and (2) if regional variation in mechanical properties is present that could support any of the postulated loading regimens. Porcine septal samples were loaded along the horizontal or vertical axes in compression and tension, using different loading rates that approximate the in vivo situation. Samples were loaded in random order to predefined strain points (2–10%) and strain was held for 30 or 120 seconds while relaxation stress was measured. Subsequently, samples were loaded until failure. Stiffness, relaxation stress and ultimate stress and strain were recorded. Results showed that the septum was stiffer, stronger and displayed a greater drop in relaxation stress in compression compared to tension. Under compression, the septum displayed non-linear behavior with greater stiffness and stress relaxation under faster loading rates and higher strain levels. Under tension, stiffness was not affected by strain level. Although regional variation was present, it did not strongly support any of the suggested loading patterns. Overall, results suggest that the septum might be mechanically capable of playing an active role in midfacial growth as evidenced by increased compressive residual stress with decreased loading rates. However, the low stiffness of the septum compared to surrounding bone does not support a strut role. The relatively low stiffness combined with high stress relaxation under fast loading rates suggests that the nasal septum is a stress dampener, helping to absorb and dissipate loads generated during mastication.     

Growth and shaping of metacarpal and carpal cartilage anlagen: application of morphometry to the development of short and long bone. A study of human hand anlagen in the fetal period

A histological and morphometric analysis of human metacarpal and carpal anlagen between the 16th and 22nd embryonic weeks was carried out with the aim of studying the establishment of the respective anlage architecture. No differences in the pattern of growth were documented between the peripheral and central zones of the metacarpal epiphyses and those of the carpals. The regulation of longitudinal growth in long bone anlagen occurred in the transition zone between the epiphysis and the diaphysis (homologous to the metaphyseal growth plate cartilage in more advanced developmental stage of the bone). Comparative zonal analysis was conducted to assess the chondrocyte density, the mean chondrocyte lacunar area, the paired chondrocyte polarity in the orthogonal longitudinal and transverse planes, and the lacunar shape transformation in the metacarpal. In transition from epiphysis to diaphysis chondrocyte density decreased and mean lacunar area increased. No significant differences in the chondrocyte maturation cycle were observed between proximal/distal metacarpal epiphyses and the carpal anlagen. The number of paired chondrocyte oriented along the growth vector was significantly higher in both proximal/distal transition zones between epiphysis and diaphysis. Human metacarpals shared with experimental models (like mice and nonmammal tetrapods) an early common chondrocyte maturation cycle but with a different timing due to the slower embryonic and fetal developmental rate of human anlagen.     

Role of microRNA-26a in cartilage injury and chondrocyte proliferation and apoptosis in rheumatoid arthritis rats by regulating expression of CTGF

This study is carried out to investigate the role of microRNA-26a (miR-26a) in cartilage injury and chondrocyte proliferation and apoptosis in rats with rheumatoid arthritis (RA) by regulating expression of CTGF. A rat model of RA induced by type II collagen was established. The rats were assigned into normal, RA, RA + mimics negative control (NC), and RA + miR-26a mimics groups, and the cells were classified into blank, mimics NC, and miR-26a mimics groups. The degree of secondary joint swelling and arthritis index, expression of miR-26a, pathological changes, proliferation and apoptosis of chondrocytes, and expression of CTGF, interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α, Bax, and Bcl-2 were also determined through a series of experiments. The targeting relationship between miR-26a and CTGF was verified. Initially, downregulated miR-26a was found in cartilage tissues and inflammatory articular chondrocytes of RA rats. In addition, CTGF was determined as a direct target gene of miR-26a, and upregulation of miR-26a inhibited CTGF expression in cartilage tissues of RA rats. Furthermore, upregulation of miR-26a reduced swelling and inflammation of joints, inhibited cartilage damage, apoptosis of chondrocytes, inflammatory injury, promotes proliferation, and inhibited apoptosis of inflammatory articular chondrocytes, which may be correlated with the targeting inhibition of CTGF expression. Collectively, the results demonstrate that upregulating the expression of miR-26a could attenuate cartilage injury, stimulate the proliferation, and inhibit apoptosis of chondrocytes in RA rats.     

Synthesis of fibronectin in normal and osteoarthritic articular cartilage

The content and the biosynthesis of fibronectin was examined in disease-free articular cartilage and in articular cartilage from osteoarthritic canine joints. Fibronectin content was increased in extracts of cartilage from osteoarthritic joints. Incubation of cartilage in vitro with [³H]phenylalanine and subsequent isolation of [³H]fibronectin from a gelatin affinity column and characterization by SDS-polyacrylamide gel electrophoresis and by immunoprecipitation indicated that disease-free and osteoarthritic cartilage explants synthesized fibronectin. About 50% of the [³H]fibronectin was recovered in the incubation medium. The osteoarthritic cartilage synthesized and accumulated up to 5-fold more [³H]fibronectin than disease-free cartilage.     

Effect of the anisotropic permeability in the frequency dependent properties of the superficial layer of articular cartilage

Abstract

Articular cartilage is a tissue of fundamental importance for the mechanics of joints, since it provides a smooth and lubricated surface for the proper transfer of loads. From a mechanical point of view, this tissue is an anisotropic poroviscoelastic material: its characteristics at the macroscopic level depend on the complex microscopic architecture. With the ability to probe the local microscopic features, dynamic nanoindentation test is a powerful tool to investigate cartilage mechanics. In this work we focus on a length scale where the time dependent behaviour is regulated by poroelasticity more than viscoelasticity and we aim to understand the effect of the anisotropic permeability on the mechanics of the superficial layer of the articular cartilage. In a previous work, a finite element model for the dynamic nanoindentation test has been presented. In this work, we improve the model by considering the presence of an anisotropic permeability tensor that depends on the collagen fibers distribution. Our sensitivity analysis highlights that the permeability decreases with increasing indentation, thus making the tissue stiffer than the case of isotropic permeability, when solicited at the same frequency. With this improved model, a revised identification of the mechanical and physical parameters for articular cartilage is provided. To this purpose the model was used to simulate experimental data from tests performed on bovine tissue, giving a better estimation of the anisotropy in the elastic properties. A relation between the identified macroscopic anisotropic permeability properties and the microscopic rearrangement of the fiber/matrix structure during indentation is also provided.     

Therapeutic effects of electromagnetic fields in the stimulation of connective tissue repair

The therapeutic effects of electric and magnetic fields have been studied largely for their promotion of connective tissue repair. The most widely studied application concerns bone repair and deals with acceleration of the healing of fresh fractures, delayed and non-unions, incorporation of bone grafts, osteoporosis, and osteonecrosis. More recently the effects of these fields upon the repair of cartilage and soft fibrous tissues have been described. In all these experimental systems and clinical applications an acceleration of extracellular matrix synthesis and tissue healing has been observed. A degree of specificity, in terms of the parameters of applied energy and biological response, is hypothesized.     

Functional role of hedgehog pathway in osteoarthritis

The hedgehog signalling pathway is one of the key regulators of metazoan development, and it plays an important role in the regulation of a variety of developmental and physiological processes. But it is aberrantly activated in many human diseases, including osteoarthritis (OA). In this study, we have reviewed the association of hedgehog signalling pathway in the development and progression of OA and evaluated the efforts to target this pathway for the prevention of OA. Usually in OA, activation of hedgehog induces up-regulation of the expression of hypertrophic markers, including type X collagen, increases production of nitric oxide and prostaglandin E2, several matrix-degrading enzymes including matrix metalloproteinase and a disintegrin and metalloproteinase with thrombospondin motifs in human knee joint cartilage leading to cartilage degeneration, and thus contributes in OA. Targeting hedgehog signalling might be a viable strategy to prevent or treat OA. Chemical inhibitors of hedgehog signalling is promising, but they cause severe side effects. Knockdown of HH gene is not an option for OA treatment in humans because it is not possible to delete HH in larger animals. Efficient knockdown of HH achieved by local delivery of small interfering RNA in future studies utilizing large animal OA models might be a more efficient approach for the prevention of OA. However, it remains a major problem to develop one single scaffold due to the different physiological functions of cartilage and subchondral bones possess. More studies are necessary to identify selective inhibitors for efficiently targeting the hedgehog pathway in clinical conditions.     

Variation in human limb joint articular morphology

Objectives

Synovial joints in human limbs strike a balance between mobility, stability, and articular fit, yet little is known about how these conflicting demands pattern intraspecific variation in articular shape. In this study, we use geometric morphometrics to establish the apportionment and magnitude of morphological variance of the articular surfaces of the human shoulder, elbow, hip, and knee. We hypothesize that variances will be comparable between articulating surfaces within a joint and will be larger in joints with smaller ranges of motion, given their plurality of functional demands.

Materials and Methods

Three-dimensional landmarks were taken on the articular surfaces of the glenohumeral, humeroulnar, acetabulofemoral, and tibiofemoral joints from CT scans of 200 skeletons from the University of Tennessee Donated Skeletal Collection (84 females, 116 males). Root mean-squared distances between articulations calculated from Procrustes shape coordinates were used to determine variance distributions.

Results

We found no difference in variances for each articular surface between the sexes or between left and right articular surfaces. A high range of motion is associated with greater morphological variance; however, this pattern is largely driven by the concave articular surfaces of each joint, which consistently exhibit statistically greater variance than their convex counterparts.

Discussion

The striking pattern of differential variance between articulating morphologies points to potential disparities in development between them. Consistently higher variance in concave surfaces may relate to chondral modeling theory for the formation of joints. Establishing intraspecific morphological variance patterns is a first step in understanding coordinated evolution among articular features.     

The optimization of a scaffold for cartilage regeneration

Natural polymers offer various advantages in cartilage tissue engineering applications, thanks to their intrinsic bioactivity and adaptability, which can be exploited for the optimization of scaffold properties. In particular, silk fibroin has multifunctional features driven by the self-assembly of molecular subunits in appropriate environmental conditions. For these reasons, it was used in combination with hyaluronic acid to produce porous sponges for cartilage regeneration. The added amount of hyaluronic acid and the cross-linking with genipin modulated scaffold properties in a synergistic way, showing a strong inter-correlation among macroscopic and microscopic characteristics. Interestingly, hyaluronic acid affected silk fibroin conformation and induced a physical separation between the two material components in absence of genipin. Instead, this was prevented by the cross-linking reaction, resulting in a more interspersed network of protein and polysaccharide molecules partially resembling the structure of cartilage extracellular matrix. In addition, the systematic evaluation of sponge properties and how they can be modulated will represent a significant starting point for the interpretation of the complex outcomes driven by the scaffold in vitro and in vivo.