Cartilaginous Structures Research Articles

Human growth plate contains aggrecan fragments that can be generated by m-calpain

Growth plate is a cartilaginous structure responsible for longitudinal growth and calcification of long bones. Aggrecan is initially expressed within the growth plate but is lost during the course of calcification. Calcium-activated proteinases are believed to play a primary role in aggrecanolysis. In this study, m-calpain was shown to be expressed in a limited area of the growth cartilage at the lower hypertrophic zone. Confocal immunostaining demonstrated colocalization of m-calpain and the aggrecan product within the lower hypertrophic chondrocytes and in limited region of the pericellular matrix. Immunoblotting analysis identified anti-VPGVA-positive aggrecan product within the dissociative fractions of A1D1–A1D6 (densities 1.65, 1.56, 1.52, 1.47, 1.41, and 1.37 g/cm3, respectively). These findings indicated that limited expression of m-calpain is colocalized with the appearance of calpain-related aggrecan products at the sites of aggrecanolysis and calcification, and suggested an important role of m-calpain in regulation of the growth plate process. The G1-G2-containing fragment of aggrecan remaining within the extracellular matrix (ECM) of the growth plate may contribute to the mechanical properties of the growth plate between the chondrocyte cell layers until bony replacement takes place.

The neural crest-enriched microRNA miR-452 regulates epithelial-mesenchymal signaling in the first pharyngeal arch

Neural crest cells (NCCs) are a subset of multipotent, migratory stem cells that populate a large number of tissues during development and are important for craniofacial and cardiac morphogenesis. Although microRNAs (miRNAs) have emerged as important regulators of development and disease, little is known about their role in NCC development. Here, we show that loss of miRNA biogenesis by NCC-specific disruption of murine Dicer results in embryos lacking craniofacial cartilaginous structures, cardiac outflow tract septation and thymic and dorsal root ganglia development. Dicer mutant embryos had reduced expression of Dlx2, a transcriptional regulator of pharyngeal arch development, in the first pharyngeal arch (PA1). miR-452 was enriched in NCCs, was sufficient to rescue Dlx2 expression in Dicer mutant pharyngeal arches, and regulated non-cell-autonomous signaling involving Wnt5a, Shh and Fgf8 that converged on Dlx2 regulation in PA1. Correspondingly, knockdown of miR-452 in vivo decreased Dlx2 expression in the mandibular component of PA1, leading to craniofacial defects. These results suggest that post-transcriptional regulation by miRNAs is required for differentiation of NCC-derived tissues and that miR-452 is involved in epithelial-mesenchymal signaling in the pharyngeal arch.

Cartilaginous Epiphyses in Extant Archosaurs and Their Implications for Reconstructing Limb Function in Dinosaurs

Extinct archosaurs, including many non-avian dinosaurs, exhibit relatively simply shaped condylar regions in their appendicular bones, suggesting potentially large amounts of unpreserved epiphyseal (articular) cartilage. This “lost anatomy” is often underappreciated such that the ends of bones are typically considered to be the joint surfaces, potentially having a major impact on functional interpretation. Extant alligators and birds were used to establish an objective basis for inferences about cartilaginous articular structures in such extinct archosaur clades as non-avian dinosaurs. Limb elements of alligators, ostriches, and other birds were dissected, disarticulated, and defleshed. Lengths and condylar shapes of elements with intact epiphyses were measured. Limbs were subsequently completely skeletonized and the measurements repeated. Removal of cartilaginous condylar regions resulted in statistically significant changes in element length and condylar breadth. Moreover, there was marked loss of those cartilaginous structures responsible for joint architecture and congruence. Compared to alligators, birds showed less dramatic, but still significant changes. Condylar morphologies of dinosaur limb bones suggest that most non-coelurosaurian clades possessed large cartilaginous epiphyses that relied on the maintenance of vascular channels that are otherwise eliminated early in ontogeny in smaller-bodied tetrapods. A sensitivity analysis using cartilage correction factors (CCFs) obtained from extant taxa indicates that whereas the presence of cartilaginous epiphyses only moderately increases estimates of dinosaur height and speed, it has important implications for our ability to infer joint morphology, posture, and the complicated functional movements in the limbs of many extinct archosaurs. Evidence suggests that the sizes of sauropod epiphyseal cartilages surpassed those of alligators, which account for at least 10% of hindlimb length. These data suggest that large cartilaginous epiphyses were widely distributed among non-avian archosaurs and must be considered when making inferences about locomotor functional morphology in fossil taxa.

Assessment and prevention of infant sleep environment hazards

Assessment and prevention of infant sleep environment hazards. Many children sleep in consumer product sleep environments, some intended for this purpose, some that are not. Infants are not just tiny...

Biological and Biomechanical Evaluations of Osteochondral Allografts Preserved in Cold Storage Solution Containing Epigallocatechin Gallate

The beneficial effects of (-)-epigallocatechin-3-O-gallate (EGCG) on the nonfrozen preservation of mammalian cells and tissues are generally not well understood. A storage solution containing EGCG was employed to test the hypothesis that EGCG is capable of extending the storage duration for the cold preservation of articular cartilages. Human articular cartilages were preserved in a storage solution composed of serum-free RPMI-1640 medium with 1% antibiotic-antimycotic solution and 1 mM EGCG at 4°C for 1, 2, and 4 weeks. The chondrocyte viability (CCK-8 assay), biochemical and immunohistochemical composition [glycosaminoglycans (GAG) and (type II) collagen], and biomechanical property (compressive elastic modulus) were assessed. The chondrocyte viability of the cartilages preserved with EGCG was significantly well maintained for at least 2 weeks with high content of GAG and total collagen. These beneficial effects of EGCG were confirmed by the immunohistochemical observations of well-preserved cartilaginous structures and delayed denaturation of the extracellular matrix in preserved cartilages. There was no significant difference in the compressive elastic modulus (MPa) between the cartilages preserved with and without EGCG. These results suggest that EGCG may play an effective role in preserving osteochondral allografts, which can be exploited in devising strategies for the long-term preservation of other tissues under cold storage conditions.

Pulmonary CT findings in relapsing polychondritis

Relapsing polychondritis (RPC) is a rare rheumatic disease characterized by recurrent inflammation of cartilaginous structures, with airway involvement a major cause of morbidity and mortality. To retrospectively evaluate airway and lung abnormalities in RPC with computed tomography (CT). From January 2004 to May 2009, 21 patients with RPC (12 men, 9 women; 13-65 years old) underwent chest CT examinations. Two chest radiologists evaluated the CT images retrospectively. Abnormal findings, including airway stenosis, airway malacia, air trapping, and airway wall thickening with or without calcifications, were observed and noted. Major abnormal CT findings were observed in eight patients (38.1%), which included airway wall thickening (n=7), airway stenosis (n=6), airway malacia (n=6), airway wall calcification (n=8), and air trapping (n=3). Mediastinal lymph nodes were found in 12 patients. Lung infection was identified in four patients and interstitial lung disease in six patients. The CT findings in patients with RPC consisted mainly of airway wall thickening, airway stenosis, airway malacia, airway wall calcification, and air trapping.

Treatment of relapsing polychondritis with the TNF-alpha antagonist adalimumab

Relapsing polychondritis (RP) is a rare immune-mediated disease which is associated with inflammation in cartilaginous tissue throughout the body. Especially, the cartilaginous structures of ear, respiratory tract, nose, and joints are affected. Around 30% of the cases are associated with other diseases especially systemic vasculitis. Onset of RP is most likely between the ages of 40-60years. This case reports the often disguised and similar symptoms of RP to Wegner's granulomatosis and the challenge of diagnosis. The relative rarity of RP has not permitted clinical trials to determine the efficacy and safety of different therapies. Current treatment is largely empiric and based on case reports. In this case, we successfully used a treatment with the TNF-alpha antagonist adalimumab.

Technical note: Terahertz imaging of ancient mummies and bone

Ancient mummified soft-tissues are a unique source to study the evolution of disease. Diagnostic imaging of such historic tissues is of foremost interest in paleoanthropology or paleopathology, with conventional x-ray and computed tomography (CT) being the gold-standard. Longer wavelength radiation in the far-infrared or Terahertz region allows diagnostic close-to-surface tissue differentiation of bone morphology while being harmless to human cells. The aim of this study is to show the feasibility and the morpho-diagnostic impact of THz imaging of historic remains. Images of an artificially embalmed ancient Egyptian human mummy hand, an artificially embalmed ancient Egyptian mummified fish and a macerated human lumbar vertebra were obtained by THz-pulse imaging and compared with conventional X-ray and CT images. Although conventional x-ray imaging provides higher spatial resolution, we found that THz-imaging is well-suited for the investigation of ancient mummified soft tissue and embalming-related substances / wrappings. In particular, bone and cartilaginous structures can be well differentiated from surrounding soft-tissues and bandage-wrappings by THz imaging. Furthermore, THz-pulse imaging also measures the time-delay of the pulsed signal when passing through the sample, which provides supplementary information on the optical density of the sample that is not obtained by X-ray and CT. Terahertz radiation provides a completely non-invasive diagnostic imaging modality for historic dry specimens. We anticipate this modality also to be used for detection of hidden objects in historic samples such as funerary amulets still in situ in wrapped mummies, as well as potentially for the identification of spectral signatures from chemical substances, e.g., in embalming essences.

The zebrafish (Danio rerio) caudal complex - a model to study vertebral body fusion

Impairment of segmentation during embryonic development leads to congenital fusion of vertebrae. Nevertheless, vertebral fusion can also occur during post-embryonic life. Fusion can cause reduction in mobility and may be pathological, but it can also be part of normal development and mechanically required, such as in the teleost caudal skeleton, or in the tetrapod sacrum. Using a series of closely spaced ontogenetic stages of zebrafish, stained for mineralized (Alizarin red) and cartilaginous (Alcian blue) structures, we have characterized all fusions occurring during the formation of the caudal skeleton. The urostyle results from the vertebral fusion of the compound centrum preural1-ural1 [PU1++U1] and ural2 [U2+]. Based on developmental and morphological characters: (i) number of vestigial haemal arches, (ii) occasional presence of a haemal arch rudiment, (iii) occasional individuals with separate centra rudiments or distinct mineralization time points, and (iv) evidence for internal separation, we propose that the urostyle forms as a fusion product of five, and not three vertebral centra, as previously described. The last fusion to occur in development, between the compound centrum [PU1++U1] and U2+, is a relatively slow process that typically occurs in Cypriniformes and Salmoniformes and is therefore considered reliable to monitor the fusion process. The vertebrae adjacent to the urostyle, preurals 2 and 3, are highly susceptible to fusion, and thus inadequate as a negative control to fusion, in contrast to trunk vertebrae, where fusion is never observed. With this we have established the basis for a new model to study vertebral fusion and to unravel cellular and molecular events underlying this process.

Uso de infliximabe na policondrite recidivante

Relapsing polychondritis (RP) is a rare systemic disease of unknown etiology, characterized by recurrent inflammation of cartilaginous structures and other connective tissues, including the ears, nose, joints, respiratory tract, and others. Due to the presence of typical signs and symptoms, biopsy is seldom necessary. Treatment includes corticosteroids, occasionally associated with immunosuppressive agents, but refractory cases are described. Recent reports suggest that anti-TNF agents, such as infliximab, may be of value in patients who do not respond to conventional therapy, but experience with this treatment is scarce. In this paper, the authors report the case of a patient with RP refractory to combined treatment with corticosteroids and immunosuppressive agents, who showed a good response to infliximab.

Surgical anatomy of cartilaginous structures of the Asian nose: Clinical implications in rhinoplasty

The morphologic features of upper and lower lateral cartilage and septal cartilage of the cadaveric nose were analyzed to provide practical anatomical knowledge for Asian rhinoplasty. Cadaveric dissection. A total of 21 Korean adult cadavers were dissected. External nasal morphology was observed, measured, photographed, and analyzed. Histologic features were observed with a light microscope in coronally-transected specimens stained with hematoxylin and eosin. The lengths of the upper and lower lateral cartilage of Korean cadaveric noses were similar to those of white noses. The widths of the upper and lower lateral cartilage were substantially smaller in Korean cadaveric noses than in those of whites. Upper lateral cartilage include substantial transverse portions near the keystone area that should be preserved in component reduction rhinoplasty. The relationships between the upper lateral cartilage and the lower lateral cartilage were divided into four types. Type I, in which the upper lateral cartilage and lower lateral cartilage are interlocked to form a Z-shape, is the most common. The posterior portion of the septal cartilage, which is connected to the perpendicular plate of the ethmoid and vomer, is thickest. Cartilaginous structures of Asian noses were substantially different from those of whites in terms of their shape, size, thickness, and relationship with other structures. The data from surgical anatomical observations of the cartilaginous framework of Korean cadaveric noses provided in this report will provide valuable information for performing rhinoplasty on Asian patients.

BONE MINERAL ULTRASTRUCTURE IN WHITE ADULT RATS UNDER THE IMPACT OF THE DIFFERENT MODES OF CHRONIC HYPERTHERMIA IN COMBINATION WITH THE PHYSICAL ACTIVITY AND POSSIBLE CORRECTION WITH INOSINE

day of interruption in a week. Loading rose step. A ventral lumbar department of rachis is studied by the methods of macro-microskopy and standard histology. Results and discussions. Amount of vascular loops at foundation of vertebrae bodies on a border with locking plates and the intervertebral disks increases after the moderate dynamic physical loadings, but goes down after the protracted loadings. Most steady to at protracted run were the intervertebral disks of reproductive animals. For impuberal animals in the conditions of the dynamic physical loadings blood vessels which in a norm absent here grow in on territory of fibrotic ring of disk intervertebral disks. Blood vessels are distributed between the fibrotic plates of fibrotic ring, but does not penetrate on territory of annulus pulposus. Growing in of blood vessels combines with distribution of dystrophic changes of fabrics of intervertebral disk, especially for old animals. Conclusion. The results of research of blood vessels of bodies of the vertebrae and border of cartilaginous structures are presented in the conditions of different on duration experimental hyperkynesia. It is set that in the conditions of the moderate loadings the level of blood vessels of bodies of the vertebrae rises and integrity of intervertebral disks is saved. Protracted loads is instrumental in the decline of level of blood supply of vertebrae and growing in the annulus fibrosus of the intervertebral disks of blood vessels with distribution in annulus fibrosus of the disk of dystrophic processes.

Nonfrozen Preservation of Articular Cartilage by Epigallocatechin-3-Gallate Reversibly Regulating Cell Cycle and NF-κB Expression

Epigallocatechin-3-O-gallate (EGCG) is known to have beneficial effects on the nonfrozen preservation of mammalian cells and tissues. In this study, we aimed at testifying the hypothesis that the deleterious effects of cold preservation of articular cartilages can be ameliorated by the addition of EGCG to the storage media. Articular cartilages were preserved in a storage solution composed of serum-free RPMI 1640 media with 1 mM EGCG at 4 degrees C for 1-4 weeks. The regulatory effects of EGCG on cell cycle progression as well as expression levels of CyCliNS (CCNs) and nuclear factor-kappaB (NF-kappaB) were investigated in articular chondrocytes. Chondrocyte viability of cartilages preserved with EGCG was significantly well maintained for 2 weeks with high contents of glycosaminoglycan and total collagen. These beneficial effects of EGCG were confirmed by histological and immunohistochemical observations showing well-preserved cartilaginous structures and delayed denaturation of extracellular matrices. The compressive elastic modulus of cartilages preserved with EGCG was close to that of fresh specimens. Increased cell population at the G(0)/G(1) phase by EGCG returned to the normal level after EGCG removal, whereas decrease at the G(2)/M phase did not. Negatively regulated expression of CCND1, CCNE2, or NF-kappaB in EGCG-treated cells was restored by removing EGCG, but not CCNA2 and CCNB1. After 8 weeks of in vivo implantation into full-thickness cartilage defects in rabbits, the cartilages preserved with EGCG were found to be integrated with the host environment and support tissue regeneration. It is suggested that EGCG plays effective roles in preserving and repairing articular cartilages by reversibly regulating cell cycle at G(0)/G(1) phase and NF-kappaB expression.

Roles of AP‐2 transcription factors in the regulation of cartilage and skeletal development

During embryogenesis, most of the mammalian skeletal system is preformed as cartilaginous structures that ossify later. The different stages of cartilage and skeletal development are well described, and several molecular factors are known to influence the events of this enchondral ossification, especially transcription factors. Members of the AP-2 family of transcription factors play important roles in several cellular processes, such as apoptosis, migration and differentiation. Studies with knockout mice demonstrate that a main function of AP-2s is the suppression of terminal differentiation during embryonic development. Additionally, the specific role of these molecules as regulators during chondrogenesis has been characterized. This review gives an overview of AP-2s, and discusses the recent findings on the AP-2 family, in particular AP-2alpha, AP-2beta, and AP-2epsilon, as regulators of cartilage and skeletal development.

Use of Sonography for Airway Assessment

The purpose of this study was to evaluate the feasibility of sonography in identifying the anatomic structures of the upper airway and to describe their appearance on sonography. We enrolled 24 healthy volunteers, placed them supine with their head extended and neck flexed (the "sniffing" position), and performed a systematic sonographic examination of their upper airway from the floor of the mouth to the suprasternal notch. We were able to visualize all relevant anatomic structures in all of the participants using either a linear or curved transducer oriented in 1 of 3 planes: sagittal, parasagittal, and transverse. Bony structures (eg, the mandible and hyoid) were brightly hyperechoic with an underlying hypoechoic acoustic shadow. Cartilaginous structures (eg, the epiglottis, thyroid cartilage, cricoid cartilage, and tracheal rings) were hypoechoic, and their intraluminal surface was outlined by a bright air-mucosa interface. The vocal cords were readily visualized through the thyroid cartilage. However, the posterior pharynx, posterior commissure, and posterior wall of the trachea could not be visualized because of artifacts created by an intraluminal air column. Sonography of the upper airway is capable of providing detailed anatomic information and has numerous potential clinical applications.

The effect of cartilaginous rings on particle deposition by convection and Brownian diffusion

The deposition of spherical nanoparticles by convection and Brownian diffusion in a pipe with a cartilaginous ring structure is studied. Analytical results for a fully developed flow are found for small amplitude rings using the interactive boundary layer theory. It is found that the local deposition rate is at maximum at a position approximately one twelfth of the spacing between the rings before the minimum cross section of the tube. For larger ring amplitudes the problem is solved numerically and separation then takes place in the depressions between the rings, and maximum deposition is found at the point of reattachment of the flow approximately at the same point as in the analytical theory. Cumulative deposition results are also provided with larger deposition rates with the inclusion of the cartilaginous rings. Deposition results for a developing flow are also provided. For the same volume flux as for fully developed flow the deposition is about 25% larger. In general conclusions about the position of maximum deposition rate from the analytic theory of fully developed flow also applies qualitatively to the case of developing flow.

High field strength magnetic resonance imaging of musculoskeletal diseases

Musculskeletal magnetic resonance imaging (MRI) applications are making the transition rapidly from 1.5 tesla (T) to 3T. The higher signal-to-noise ratio (SNR) that is available with a 3T MRI system allows for greater spatial resolution and provides the potential to improve the diagnostic capability of musculoskeletal MRI. With the use of 3T systems, one can enhance the SNR, spatial resolution, and contrast-to-noise ratio of intrinsic joint structures such as osseous, tendinous, cartilaginous, and ligamentous structures, which makes them more discernable and amenable to proper radiologic assessment. The SNR gain and coil technology advances allow for a smaller voxel-size and parallel imaging, reducing the acquisition time without significant signal loss. Three-dimensional (3D) fast spin echo sequences with isotropic resolution reduce partial volume artifacts through the acquisition of thin continuous sections and enable free 3D-multi-planar-reformatting without loss of image quality. This technique may be a promising method to replace currently used 2D sequences in clinical practice. In addition to current clinical applications, 3T MRI will contribute to the development of new molecular and functional MRI techniques.

Highly differentiated sacrococcygeal teratoma.

Sacrococcygeal teratoma is a well known entity and both its diagnosis and management have been thoroughfully described. Special mention deserves the highly differentiated teratoma as it presents complex organized tissular structures making it slightly different from the classic teratoma although it does not reach the defining characteristics of fetus-in-fetu.A female newborn without prenatal diagnosis presented sacro-coccygeal mass. X-ray image showed bone structures resembling tibia and fibula within the mass. She undertook surgery two days after delivery. Macroscopically, the mass showed besides the bones described on X ray image, cartilaginous structures, some loops of bowel and tissue resembling a finger. There were also some cystic areas. Highly differentiated teratoma also called fetiform teratoma seems to be a defined entity apart from the classical sacrococcygeal teratoma and the fetus-in-fetus. However differences regarding physiopathological and clinical aspects have not been yet completely described.

Fetal MR imaging of Kniest dysplasia

We present a case of Kniest dysplasia, a rare form of the type II collagenopathies, with prenatal MRI. Sonography revealed only short limbs in the fetus. Fetal MRI findings included enlarged hyaline cartilaginous structures with abnormally high T2 signal intensity, delayed ossification of the pubic and ischial bones, and platyspondyly. By delineating the cartilaginous abnormalities, fetal MRI can contribute to the prenatal diagnosis of chondrodysplasias.

Transient Activation of Wnt/β-Catenin Signaling Induces Abnormal Growth Plate Closure and Articular Cartilage Thickening in Postnatal Mice

Wnt/beta-catenin signaling is required for skeletal development and organization and for function of the growth plate and articular cartilage. To further clarify these roles and their possible pathophysiological importance, we created a new transgenic mouse model in which Wnt/beta-catenin signaling can be activated in cartilage for specific periods of time. These transgenic mice expressed a constitutive active form of beta-catenin fused to a modified estrogen receptor ligand-binding domain under the control of cartilage-specific collagen 11alpha2 promoter/enhancer. Transient Wnt/beta-catenin signaling activation in young adult mice by tamoxifen injections induced growth retardation and severe deformities in knee joints. Tibial and femoral growth plates displayed an excessive number of apoptotic cells and eventually underwent abnormal regression. Articular cartilage exhibited an initial acute loss of proteoglycan matrix that was followed by increases in thickness, cell density, and cell proliferation. In reciprocal studies, we found that conditional ablation of beta-catenin in postnatal mice using a Col2-CreER strategy led to hypocellularity in articular cartilage, growth plate disorganization, and a severe reduction in bone volume. Together, these data provide evidence that Wnt/beta-catenin signaling has important and distinct roles in growth plate and articular cartilage and that postnatal dysregulation of this signaling pathway causes diverse structural and functional changes in the two cartilaginous structures.