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ABSTRACT: This investigation was designed to unravel gene networks in Kashin-Beck disease (KBD) and better identify target genes of KBD for gene therapy development. RNA was isolated separately from cartilage and peripheral blood samples of patients with KBD and healthy controls. Agilent 44K human whole-genome oligonucleotide microarrays were used to detect differentially expressed genes. Three significant canonical pathways and nine chondrocyte networks from chondrocytic gene expression profiles were screened using ingenuity pathway analysis (IPA), but only one network and no canonical pathways from peripheral blood monocytic gene profile were identified. Bak1, APAF-1, CASP6, IGFBP2, Col5a2 and TGFBI extracted from significant genes that involved in chondrocytic canonical pathways and networks may have closer relationship with the etiopathogenesis of KBD. Those genes may be potential targets for gene diagnosis and treatment. Six physiological functions were predominant and unique to the chondrocytic genes, whereas two were unique to peripheral blood monocytic genes. The identified genes may represent a source of potentially novel molecular targets, which may provide a better understanding of the molecular details in KBD pathogenesis and also provide useful pathways and network maps for the future research in osteochondrosis.
Genes to Cells 07/2012; 17(8):619-32. · 2.68 Impact Factor
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ABSTRACT: To investigate the differences between the gene expression profiles in peripheral blood mononuclear cells (PBMC) from normal controls and patients with Kashin-Beck disease (KBD).
Twenty KBD patients and 12 normal subjects were selected from a KBD-endemic area and divided into four pairs of KBD vs. control (KBD, n = 5 per pair; control, n = 3 per pair). RNAs were respectively isolated from KBD PBMCs and normal PBMCs. Gene expression profiles were analyzed by oligonucleotide microarray. The gene expression profiles in PBMCs from KBD patients and normal controls were compared and the differentially expressed genes were identified. The obtained microarray data was further confirmed by using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR).
Approximately 501 genes, corresponding to 2.4% of the total probe transcripts, showed a 2-fold change in differential expression. 19.4% (97 out of 501)of the differentially expressed genes were commonly detected in all the four pairs. Among the 97 differentially expressed genes, 83 genes were up-regulated and 14 genes were down-regulated, compared with those in the normal controls. Some differentially expressed genes were found to be related to functions such as immunity, metabolism, apoptosis, cystoskeleton and cell movement, and extracellular matrix. The validity of our microarray data were supported by the results of qRT-PCR assay.
Differences in the PBMC gene expression profile between the KBD patients and the normal controls exhibited a similar pattern among all the four pairs of microarrays examined, indicating that the suppressed immunity may play an important role in the pathogenesis of KBD.
PLoS ONE 01/2012; 7(1):e28439. · 4.09 Impact Factor
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ABSTRACT: The purpose of the current study was to investigate the changes of serum proteome and discover potential biomarkers for Kashin-Beck disease (KBD) using surface-enhanced laser desorption ionization mass spectrometry (SELDI-TOF MS). The serum protein profiles from 102 cases (36 KBD patients, 16 controls in KBD areas, 33 controls in non-KBD areas, and 17 osteoarthritis controls) were detected by SELDI-TOF MS and weak cation-exchange protein chip. Differently expressed peaks in KBD were identified by comparing the data among the four groups using the nonparametric Mann-Whitney test with Bonferroni correction at a significance level of 0.05. Then, those 102 cases were used to generate a classification tree as the training set, and an additional 34 cases were collected as the test set. A classification tree was generated by Biomarker Patterns Software (Ciphergen). Multiple protein changes were detected in the KBD group, including three potential biomarkers (15 886, 5336, 6113 m/z). A classification tree with three distinct proteins was generated. The classification tree was able to distinguish the KBD patients from the controls with 88.89% specificity and 86.36% sensitivity. The study demonstrates that marked serum proteomic changes exist in KBD. The proteins represented by the differently expressed peaks are candidate biomarkers for KBD.
Journal of Bone and Mineral Metabolism 02/2008; 26(4):385-93. · 2.27 Impact Factor
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ABSTRACT: To investigate the association of serum levels of hyaluronic acid (HA), tumor necrosis factor-alpha (TNF-alpha), vascular endothelial growth factor (VEGF), NO, and Se with the clinical manifestations in adult patients with Kashin-Beck disease (KBD).
Total 216 adults were selected for KBD screening from the KBD-prevalent areas in Yongshou county and the non-KBD areas of Chang'an county, Xi'an city, ShaanXi Province. According to the National Diagnostic Criteria of Kashin-Beck Disease in China, the diagnoses of KBD was established in 25 adult patients (11 men and 14 women, average age of 47.88+/-11.16 years), and 20 healthy control subjects from the KBD areas (8 men and 12 women, average age of 47.85+/-12.05 years) and 20 from the non-KBD areas (8 men and 12 women, average age of 47.45+/-11.24 years) were also selected to serve as controls. There was no significant difference in the average age and gender distribution between the 3 groups. The serum levels of HA, TNF-alpha, VEGF, NO and Se were measured by enzyme-linked immunosorbent assay, nitrate reductase method and griphite furnace atomic absorption spectrometry.
Serum NO level was significantly higher in KBD group (41.7+/-21.89 micromol/L) than in the health controls from KBD areas (17.1+/-13.01 micromol/L) and non-KBD areas (17.58+/-11.48 micromol/l, F=13.11, df=2, P<0.001). Serum TNF-alpha level in KBD group (32.7+/-3.55 pg/ml) was significantly higher than that in the control subjects from the non-KBD areas (30.95+/-2.22 pg/ml, F=3.672, df=2, P=0.031), but similar with the control subjects from the KBD areas (32.7+/-3.55 pg/ml). Serum TNF-alpha and NO levels were identified as the indices that differed between adult KBD patients and the controls from both KBD and non-KBD areas by differential analysis (the function of differentiation was 0.062xNO+0.173xTNF -7.218).
Serum TNF-alpha and NO levels are significantly increased in adult KBD patients and are associated with the clinical manifestations of KBD.
Nan fang yi ke da xue xue bao = Journal of Southern Medical University 07/2007; 27(7):941-4.
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ABSTRACT: To explore the significance of genetic factor in the pathogenesis of skeletal angle III malocclusion.
A case-control study of 96 probands, 200 controls and their relatives was performed and the data were analyzed with genetic epidemiologic methods. SPSS11.5 software package was used for Chi-square test.
The prevalence rates of skeletal angle III malocclusion in the first-degree relatives and second-degree relatives in the proband group were 9.00% and 1.88%,respectively,which were higher than that in the first-degree relatives in the control group(0.96%). The heritability in the first-degree relatives was 0.74+/-0.092.The results of segregation analysis didn't suggest that skeletal angle III malocclusion followed a pattern of autosomal recessive inheritance.
Skeletal angle III malocclusion has characteristics of polygenetic disease. Genetic factor might play an important role in the pathogenesis of skeletal angle III malocclusion.
Shanghai kou qiang yi xue = Shanghai journal of stomatology 07/2006; 15(3):269-72.
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ABSTRACT: To study histological changes under the conditions of orthodontic rapid tooth movement through distraction osteogenesis of the periodental ligament on dogs.
The experiment was carried out in 6 dogs, the left side of jaws of each one was set as test or control side, and the other side was control or test side. On the control side, the first premolar was moved using traditional methods while the third premolar as anchor, on the test side, using self-made distraction device. The periodental tissue of tooth moved were extracted at the end of the test, some of decalcified sections were stained with hematoxylin and eosin and others with modified Mallory's trichrome staining method, being examined by LM.
Decalcified sections stained with hematoxylin and eosin showed the bone formed actively, and there were a large number of fibroblasts and osteoblasts as well as abundant vascularity. The modified Mallory's trichrome staining method showed the newly formed bone very clearly and distinctly.
There was no difference in quality but in quantity on the histological reactions in tension side of the tooth moved by traditional method and by distraction osteogenesis through the peridental ligament and periodontal membrane, the latter could induce higher activity of histological synthesization than the former.
Shanghai kou qiang yi xue = Shanghai journal of stomatology 09/2004; 13(4):312-4.
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Shanghai kou qiang yi xue = Shanghai journal of stomatology 07/2003; 12(3):234, 238.
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ABSTRACT: Kashin-Beck disease (KBD) is a degenerative osteoarticular disease of unknown etiology. The management of KBD would benefit from the identification of the biomarkers related to this disease. In this study, mass spectrometry (MS)-based proteomic profiling was used to identify potential biomarkers of the disease. One hundred and sixteen serum samples of KBD cases and healthy controls were collected and analyzed. A framework for data analysis was implemented, which included normalization, denoising using undecimated discrete wavelet transforms, baseline subtraction, peak detection and alignment, non-parametric testing and classification by support vector machine. The method identified correlative mass points and obtained a discriminative pattern with 90.91% sensitivity and 82.61% specificity. The results of this study, although preliminary, suggest that further proteomics study may be useful with a larger number of appropriate specimens, careful experiment manipulation and improved MS techniques.
Molecular Medicine Reports 3(5):821-4. · 0.42 Impact Factor