Effect of Bilateral Mandibular Osteodistration on the Condylar Cartilage: An Experimental Study on Rabbits

Although various aspects of bone formation during distraction osteogenesis have been studied extensively, there are only limited experimental data concerning the influence of hyper-physiologic mandibular distraction rate on structural alterations in the temporomandibular joint (TMJ) condylar cartilage. The purpose of this study was to evaluate the effect of bilateral distraction osteogenesis of the mandibular body, at a hyper-physiologic rate and length, on the integrity of the condylar cartilage in rabbits. MATERIALS AND METHODS: Eighteen healthy adult male rabbits weighing 2 to 3 kg were assigned to 1 of 2 groups: the control group (n = 2 rabbits, 4 joints) or the study group (n = 16 rabbits, 32 joints) four rabbits (8 joints) in each subgroup according to the post-distraction period (1,2,3 or 4 weeks). In the control group, rabbits received sham surgery (Osteotomy without distraction) and then left to live for 4 weeks under the same condition of the study group then euthanized using intravenous overdose of pentobarbital sodium. In the study group, an extra oral custom-made distracter was employed to achieve bilateral mandibular hyper physiologic distraction (1.5 mm twice daily for 5 days) distraction. All animals were evaluated clinically and histomorphometrically and results analyzed by MINITABE 13.1 statistical package using ANOVA test. RESULTS: Animals underwent distraction showed obvious changes in condylar surface contour related to length of the follow up period, compared to the control; these changes seemed to be partly reversible. The most pronounced observation was the irregularities and resorption in the anterior part of the condylar cartilage and the subcondylar bone. Moreover, at the first two weeks, the area of resorption was invaded by large number of osteoclasts and chronic inflammatory cells which declined later in the 3rd and 4th weeks and replaced with osteoblastic activities. CONSLUSION: These experimental data showed that distraction rate of 3 mm per day may lead to degenerative or even early arthritic changes in the TMJ condylar cartilage in the 1st and 2nd post-distraction weeks. However, all condyles showed adaptive and remodeling sings in the following 3rd and 4th weeks

Urinary Extracellular Domain of Neurotrophin Receptor p75 as a Biomarker for Amyotrophic Lateral Sclerosis in a Chinese cohort

To comprehensively assess whether p75ECD in urine could be a candidate biomarker for ALS evaluation. Urine samples were collected from 101 ALS patients, 108 patients with other neurological disease (OND) and 97 healthy controls. 61 ALS patients were followed up with clinical data including ALSFRS-r every 6 to 12 months, 23 ALS patients died and 17 ALS patients lost touch during follow up period. Enzyme-linked immunoassay was employed to determine urine p75ECD concentration. The ALSFRS-r was employed to assess the severity of ALS. The concentration of p75ECD in ALS was significantly higher than that of OND and CTRL (p < 0.001). Additionally, urine p75ECD concentrations in ALS-definite grade patients were significantly higher than that in ALS-probable grade and ALS-possible grade patients (p < 0.001). Higher urine p75ECD concentrations were correlated with increased clinical stage (p = 0.0309); urine p75ECD concentrations and ALSFRS-r were negatively correlated (p = 0.022); and urine p75ECD concentration in the fast-progressing ALS group was significantly higher than that in slow-progression (p = 0.0026). Our finding indicates that urine p75ECD concentration provides additional evidence for patients with clinically suspected ALS, and can be employed to evaluate ALS-severity

Effects of peripheral nerve injury on parvalbumin expression in adult rat dorsal root ganglion neurons

Background: Parvalbumin (PV) is a calcium binding protein that identifies a subpopulation of proprioceptive dorsal root ganglion (DRG) neurons. Calcitonin gene-related peptide (CGRP) is also expressed in a high proportion of muscle afferents but its relationship to PV is unclear. Little is known of the phenotypic responses of muscle afferents to nerve injury. Sciatic nerve axotomy or L5 spinal nerve ligation and section (SNL) lesions were used to explore these issues in adult rats using immunocytochemistry. Results: In naive animals, the mean PV expression was 25 % of L4 or L5 dorsal root ganglion (DRG) neurons, and this was unchanged 2 weeks after sciatic nerve axotomy. Colocalization studies with the injury marker activating transcription factor 3 (ATF3) showed that approximately 24 % of PV neurons expressed ATF3 after sciatic nerve axotomy suggesting that PV may show a phenotypic switch from injured to uninjured neurons. This possibility was further assessed using the spinal nerve ligation (SNL) injury model where injured and uninjured neurons are located in different DRGs. Two weeks after L5 SNL there was no change in total PV staining and essentially all L5 PV neurons expressed ATF3. Additionally, there was no increase in PV-ir in the adjacent uninjured L4 DRG cells. Co-labelling of DRG neurons revealed that less than 2 % of PV neurons normally expressed CGRP and no colocalization was seen after injury. Conclusion: These experiments clearly show that axotomy does not produce down regulation of PV protein in the DRG. Moreover, this lack of change is not due to a phenotypic switch in PV immunoreactive (ir) neurons, or de novo expression of PV-ir in uninjured neurons after nerve injury. These results further illustrate differences that occur when muscle afferents are injured as compared to cutaneous afferents

Identification of a Gene Regulatory Network Necessary for the Initiation of Oligodendrocyte Differentiation

Differentiation of oligodendrocyte progenitor cells (OPCs) into mature oligodendrocytes requires extensive changes in gene expression, which are partly mediated by post-translational modifications of nucleosomal histones. An essential modification for oligodendrocyte differentiation is the removal of acetyl groups from lysine residues which is catalyzed by histone deacetylases (HDACs). The transcriptional targets of HDAC activity within OPCs however, have remained elusive and have been identified in this study by interrogating the oligodendrocyte transcriptome. Using a novel algorithm that allows clustering of gene transcripts according to expression kinetics and expression levels, we defined major waves of co-regulated genes. The initial overall decrease in gene expression was followed by the up-regulation of genes involved in lipid metabolism and myelination. Functional annotation of the down-regulated gene clusters identified transcripts involved in cell cycle regulation, transcription, and RNA processing. To define whether these genes were the targets of HDAC activity, we cultured rat OPCs in the presence of trichostatin A (TSA), an HDAC inhibitor previously shown to inhibit oligodendrocyte differentiation. By overlaying the defined oligodendrocyte transcriptome with the list of ‘TSA sensitive’ genes, we determined that a high percentage of ‘TSA sensitive’ genes are part of a normal program of oligodendrocyte differentiation. TSA treatment increased the expression of genes whose down-regulation occurs very early after induction of OPC differentiation, but did not affect the expression of genes with a slower kinetic. Among the increased ‘TSA sensitive’ genes we detected several transcription factors including Id2, Egr1, and Sox11, whose down-regulation is critical for OPC differentiation. Thus, HDAC target genes include clusters of co-regulated genes involved in transcriptional repression. These results support a de-repression model of oligodendrocyte lineage progression that relies on the concurrent down-regulation of several inhibitors of differentiation

Differential Deployment of REST and CoREST Promotes Glial Subtype Specification and Oligodendrocyte Lineage Maturation

The repressor element-1 (RE1) silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) is a master transcriptional regulator that binds to numerous genomic RE1 sites where it acts as a molecular scaffold for dynamic recruitment of modulatory and epigenetic cofactors, including corepressor for element-1-silencing transcription factor (CoREST). CoREST also acts as a hub for various cofactors that play important roles in epigenetic remodeling and transcriptional regulation. While REST can recruit CoREST to its macromolecular complex, CoREST complexes also function at genomic sites independently of REST. REST and CoREST perform a broad array of context-specific functions, which include repression of neuronal differentiation genes in neural stem cells (NSCs) and other non-neuronal cells as well as promotion of neurogenesis. Despite their involvement in multiple aspects of neuronal development, REST and CoREST are not believed to have any direct modulatory roles in glial cell maturation.We challenged this view by performing the first study of REST and CoREST in NSC-mediated glial lineage specification and differentiation. Utilizing ChIP on chip (ChIP-chip) assays, we identified distinct but overlapping developmental stage-specific profiles for REST and CoREST target genes during astrocyte (AS) and oligodendrocyte (OL) lineage specification and OL lineage maturation and myelination, including many genes not previously implicated in glial cell biology or linked to REST and CoREST regulation. Amongst these factors are those implicated in macroglial (AS and OL) cell identity, maturation, and maintenance, such as members of key developmental signaling pathways and combinatorial transcription factor codes.Our results imply that REST and CoREST modulate not only neuronal but also glial lineage elaboration. These factors may therefore mediate critical developmental processes including the coupling of neurogenesis and gliogenesis and neuronal-glial interactions that underlie synaptic and neural network plasticity and homeostasis in health and in specific neurological disease states

Primary and secondary cartilages of the neonatal rat: the femoral head and the mandibular condyle.

Contains fulltext : 57688.pdf (publisher's version ) (Closed access)Primary and secondary cartilages differ in embryonic origin and in histological organization, and are generally considered to have a different mode of growth. However, few studies have directly compared the two types of cartilage of the same animal at the same age. Therefore, we analysed several histological and biochemical differences between secondary cartilage of the mandibular condyle and primary cartilage of the femoral head of 4-d-old rats. We evaluated the tissue organization, the level of DNA and glycosaminoglycan (GAG) synthesis, and the GAG and collagen content. The expression of collagen types I, II and III and of receptors for insulin-like growth factor (IGF)-I, fibroblast growth factor (FGF), and transforming growth factor (TGF)-beta were investigated by immunohistochemistry. The ex vivo DNA and GAG synthesis as well as the GAG content of femoral heads were much higher than that of mandibular condyles. Mandibular condyles expressed both collagen types I and II, while femoral heads expressed only type II collagen. In the mandibular condyles, receptors for IGF-I, FGF, and TGF-beta were observed mainly in the superficial layers, whereas they were found throughout the entire femoral head. In conclusion, major differences were found between both types of cartilage, which might be related to their specific functional demands