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 28,634 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

NG2 cells (polydendrocytes) comprise an abundant glial population that is widely and uniformly distributed throughout the developing and mature CNS and are identified by the expression of the NG2 proteoglycan at the cell surface. Although recent electrophysiological studies suggest that they are capable of receiving signals from axon terminals, other studies, based on the finding that the NG2 molecule itself induces growth cone collapse, have led to a widely held speculation that NG2 cells themselves also repel and inhibit growing axons. In this study, we have examined the effects of rat NG2 cells on growing hippocampal and neocortical axons in vitro and in vivo. NG2 cells did not repel growing axons but promoted their growth in vitro, and axonal growth cones formed extensive contacts with NG2 cells both in vitro and in the developing corpus callosum. Punctate immunoreactivity for fibronectin and laminin was found to be colocalized with NG2 on the surface of NG2 cells. Altering the level of cell surface NG2 expression had no effect on the growth-promoting effects of NG2 cells on growing axons. Thus, our study indicates that NG2 cells are not inhibitory to growing axons but provide an adhesive substrate for axonal growth cones and promote their growth even in the presence of elevated levels of the NG2 proteoglycan. These findings suggest a novel role for NG2 cells in facilitating axonal growth during development and regeneration.
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PMID:NG2 glial cells provide a favorable substrate for growing axons. 1682 34

The purpose of this paper is to review the scientific literature on the natural history of bone bruises and the experimental studies regarding the histopathological effects of impaction load on articular cartilage and subchondral bone. Bone bruises with subchondral or osteochondral injuries, or geographic bone bruises seemed to be persistent for years after trauma on MRI. Biopsy samples of the articular cartilage overlying the bone bruise lesions showed degeneration or necrosis of chondrocytes and loss of proteoglycan. Experimental studies using a single impact load revealed chondrocytes death, alteration of the mechanical properties of cartilage explants and/or an increase in the thickness of subchondral bone. These data are indicative of a significant injury to normal articular cartilage homeostasis, and support the suggestion that severe bone bruise is a precursor of early degenerative changes. We recommend delaying return to full weightbearing status when a severe bone bruise is detected to prevent further collapse of subchondral bone and further aggravation of articular cartilage injury.
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PMID:Natural history of bone bruises after acute knee injury: clinical outcome and histopathological findings. 1678 36

Aggrecan is one of the major chondroitin sulfate proteoglycans (CSPGs) expressed in the central nervous system. The signaling pathways activated downstream of cell interaction with aggrecan and with CSPGs in general and the importance of chondroitin sulfate-glycosaminoglycan side chains in their inhibition are unclear. Therefore, to analyze the effect of different components of aggrecan in inhibiting neurite growth, neurite outgrowth was quantified in an in vitro model in which chick dorsal root ganglion (DRG) explants were grown on substrates containing aggrecan bound to hyaluronan and link protein as a macromolecular aggregate, aggrecan monomers, hyaluronan, or ChABC-treated aggrecan. Aggrecan aggregate, aggrecan monomer, and hyaluronan inhibited neurite outgrowth from nerve growth factor (NGF)- and neurotrophin-3 (NT3)-responsive DRG neurons. Aggrecan inhibition was dependent on its chondroitin sulfate-glycosaminoglycans, as ChABC digestion alleviated neurite inhibition because of aggrecan. Growth cones displayed full or partial collapse on aggrecan aggregate, hyaluronan, and ChABC-treated aggrecan. Inhibition of Rho kinase (ROCK) with Y27632 increased neurite growth on some but not all of the aggrecan components tested. With NGF in the culture medium, Y27632 increased neurite outgrowth on aggrecan aggregate, monomers, and ChABC-treated aggrecan, but not on hyaluronan. The ROCK inhibitor also increased NT3-responsive outgrowth on aggrecan aggregate and hyaluronan, but not on ChABC-treated aggrecan. This study showed that the matrix proteoglycan aggrecan and its components have multiple effects on neurite outgrowth and that some of these effects involve the Rho/ROCK pathway.
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PMID:Aggrecan components differentially modulate nerve growth factor-responsive and neurotrophin-3-responsive dorsal root ganglion neurite growth. 1791 43

To study the effectiveness of pomegranate juice on osteoarthritis, mono-iodoacetate induced loss of articular cartilage in the mouse tibiofemoral joint was used as a model. Mono-iodoacetate is an inhibitor of glycolysis which promotes osteoarthritis similar to that noted in human osteoarthritis. The histopathology of the subchondral bone and cartilage of mouse knee joints treated with a single intra-articular injection of mono-iodoacetate (0.1 mg) and killed at 1, 14 and 28 days post injection was investigated. The effect of pomegranate juice (4 mL/kg, 10 mL/kg, 20 mL/kg, orally) was studied in different groups. Histopathological changes in knee joints were seen after 2 weeks. Early osteoarthritis was characterized by areas of chondrocyte degeneration, which sometimes involved the entire thickness of the articular cartilage in the tibial plateaus and femoral condyles. Changes to the subchondral bone and proteoglycan contents, focal fragmentation and collapse of bony trabeculae with fibrosis and necrosis, and synovial cell proliferation were observed. The administration of pomegranate juice dose dependently prevented the negative effects of iodoacetate. Chondrocyte damage was significantly prevented, with proteoglycan less affected, especially in the groups receiving a high amount of pomegranate juice. No cell proliferation or inflammatory cells were detected in the synovial fluid. The effectiveness of pomegranate juice in improving histopathological damage is emphasized and its chondroprotective effect in vivo highlighted.
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PMID:Chondroprotective effects of pomegranate juice on monoiodoacetate-induced osteoarthritis of the knee joint of mice. 1950 67

The relatively thin cartilage of the hip joint, as well as its complex geometry, poses challenges for standardized, reproducible assessment of cartilage and the acetabular labrum. With appropriate pulse sequence parameters, however, accurate, reproducible assessment of cartilage and the labrum is feasible. More detailed evaluation of cartilage biochemistry may be obtained with techniques aimed at noninvasively evaluating the integrity of collagen and/or proteoglycan components in the articular cartilage. One of the benefits of noncontrast techniques lie in the ability to visualize the native synovium, and thereby detect the presence of synovial proliferative disorders, the clinical symptoms of which may mimic a labral tear or traumatic cartilage injury. Standard cartilage evaluation allows for the detection of surface delamination and osteoarthritis in the setting of femoroacetabular impingement, as well as subtle areas of subchondral collapse and secondary delamination of cartilage in the setting of osteonecrosis. This preserves the use of hip arthroscopy as a therapeutic rather than a diagnostic tool.
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PMID:High resolution noncontrast MRI of the hip. 2009 38

Oligodendrocyte myelin glycoprotein (OMgp) is expressed by both neurons and oligodendrocytes in the CNS. It has been implicated in growth cone collapse and neurite outgrowth inhibition by signaling through the Nogo receptor and paired Ig-like receptor B (PirB). OMgp was also reported to be an extracellular matrix (ECM) protein surrounding CNS nodes of Ranvier and proposed to function as (1) an inhibitor of nodal collateral sprouting and (2) an important contributor to proper nodal and paranodal architecture. However, we show here that the anti-OMgp antiserum used in previous studies to define the functions of OMgp at nodes is not specific. Among all reported nodal ECM components, the antiserum exhibited strong cross-reactivity against versican V2 isoform, a chondroitin sulfate proteoglycan. Furthermore, the OMgp antiserum labeled OMgp-null nodes, but not nodes from versican V2-deficient mice, and preadsorption of the OMgp antiserum with recombinant versican V2 blocked nodal labeling. Analysis of CNS nodes in OMgp-null mice failed to reveal any nodal or paranodal defects, or increased nodal collateral sprouting, indicating that OMgp does not participate in CNS node of Ranvier assembly or maintenance. We successfully identified a highly specific anti-OMgp antibody and observed OMgp staining in white matter only after initiation of myelination. OMgp immunoreactivity decorated the surface of mature myelinated axons, but was excluded from compact myelin and nodes. Together, our results strongly argue against the nodal localization of OMgp and its proposed functions at nodes, and reveal OMgp's authentic localization relative to nodes and myelin.
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PMID:Oligodendrocyte myelin glycoprotein does not influence node of ranvier structure or assembly. 2098 Jun 5

Unlike mammals, fish are able to regenerate axons in their central nervous system. This difference has been partly attributed to the loss/acquisition of inhibitory proteins during evolution. Nogo-A--the longest isoform of the reticulon4 (rtn4) gene product--is commonly found in mammalian myelin where it acts as a potent inhibitor of axonal regeneration. Interestingly, fish RTN4 isoforms were previously reported to lack the most inhibitory Nogo-A-specific region (NSR). Nevertheless, fish axons collapse on contact with mammalian NSR, suggesting that fish possess a functional Nogo-A receptor but not its ligand. To reconcile these findings, we revisited the early evolution of rtn4. Mining of current genome databases established the unequivocal presence of NSR-coding sequences in fish rtn4 paralogues. Further comparative analyses indicate that the common ancestor of fish and tetrapods had an NSR-coding rtn4 gene, which underwent duplication and divergent evolution in bony fish. Our genomic survey also revealed that the cephalochordate Branchiostoma floridae contains a single rtn gene lacking the NSR. Hence, Nogo-A most probably arose independently in the rtn4 gene of a gnathostome ancestor before the split of the fish and tetrapod lineages. Close examination of the NSR uncovered clusters of structural and sequential similarities with neurocan (NCAN), an inhibitory proteoglycan of the glial scar. Notably, the shared presence of transposable elements in ncan and rtn4 genes suggests that Nogo-A originated via insertion of an ncan-like sequence into the rtn4 gene of an early jawed vertebrate with myelinated axons.
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PMID:Origin of Nogo-A by domain shuffling in an early jawed vertebrate. 2109

Peanut agglutinin-binding disaccharides and chondroitin sulfate mark transient mesenchymal barriers to advancing motor and sensory axons innervating the hindlimbs during chick development. Here we show that the vast majority of these carbohydrates are at the critical stage and location attached to the versican splice variants V0 and V1. We reveal that the isolated isoforms of this extracellular matrix proteoglycan suppress axon extension at low concentrations and induce growth cone collapse and rapid retraction at higher levels. Moreover, we demonstrate that versican V0 and/or V1, recombinantly expressed in collagen-I gels or ectopically deposited in the hindlimbs of chicken embryos in ovo, cause untimely defasciculation and axon stalling. Consequently, severe disturbances of nerve patterning are observed in the versican-treated embryos. Our experiments emphasize the inhibitory capacity of versicans V0 and V1 in axonal growth and evidence for their function as basic guidance cues during development of the peripheral nervous system.
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PMID:Versican V0 and V1 direct the growth of peripheral axons in the developing chick hindlimb. 2147 61

Episodic falling syndrome (EFS) is a canine paroxysmal hypertonicity disorder found in Cavalier King Charles spaniels. Episodes are triggered by exercise, stress or excitement and characterized by progressive hypertonicity throughout the thoracic and pelvic limbs, resulting in a characteristic 'deer-stalking' position and/or collapse. We used a genome-wide association strategy to map the EFS locus to a 3.48 Mb critical interval on canine chromosome 7. By prioritizing candidate genes on the basis of biological plausibility, we found that a 15.7 kb deletion in BCAN, encoding the brain-specific extracellular matrix proteoglycan brevican, is associated with EFS. This represents a compelling causal mutation for EFS, since brevican has an essential role in the formation of perineuronal nets governing synapse stability and nerve conduction velocity. Mapping of the deletion breakpoint enabled the development of Multiplex PCR and Multiplex Ligation-dependent Probe Amplification (MLPA) genotyping tests that can accurately distinguish normal, carrier and affected animals. Wider testing of a larger population of CKCS dogs without a history of EFS from the USA revealed that carriers are extremely common (12.9%). The development of molecular genetic tests for the EFS microdeletion will allow the implementation of directed breeding programs aimed at minimizing the number of animals with EFS and enable confirmatory diagnosis and pharmacotherapy of affected dogs.
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PMID:A canine BCAN microdeletion associated with episodic falling syndrome. 2182 Nov 25

We have shown that draxin is a repulsive axon guidance molecule for a variety of neuron classes and that genetic deletion of draxin in mice results in the absence of all forebrain commissures. Moreover, we also identified a secreted molecule, Tsukushi (TSK), that belongs to the small leucine-rich proteoglycan family (SLRP) and inhibits signaling molecules, such as BMP and Wnt. TSK knockout mice show malformation of the corpus callosum (CC) and agenesis of the anterior commissure (AC), suggesting the importance of TSK function in forebrain commissure formation. There is a possibility that the combined function of these two proteins is essential for the formation of these commissures. In this study, we investigate this possibility by generating draxin/TSK doubly heterozygous mice and comparing their forebrain commissure phenotypes with those of singly heterozygous mice. We found that, although draxin and TSK did not interact directly, their genetic interaction was evident from the significantly higher prevalence of CC malformation and agenesis of the AC in the draxin/TSK doubly heterozygous mice. Importantly, in this study, we demonstrated a new function of TSK in guiding anterior olfactory neuronal (AON) and cortical axons. TSK bound to and provided growth inhibitory signals dose-dependently to AON and cortical axons in outgrowth assay. TSK also induced growth cone collapse when applied acutely to these cultured neurons. Furthermore, TSK and draxin had additive effects in inhibiting cortical and AON neurite outgrowth. Thus, based on a combination of genetic analyses and in vitro experiments, we propose that the combined guidance activities of draxin and TSK regulate forebrain commissure formation.
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PMID:The combinatorial guidance activities of draxin and Tsukushi are essential for forebrain commissure formation. 2320 92


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