Differential expression of cyclins CCNB1 and CCNG1 is involved in the chondrocyte damage of kashin-beck disease

The purpose of this study was clarify the relationship between the differential expression of cyclins CCNB1 and CCNG1 and chondrocyte damage in Kashin-Beck disease. Systematic review and high-throughput sequencing of chondrocytes derived from Kashin-Beck disease patients were combined to identify the differentially expressed cyclins and cyclin-dependent kinase genes. In parallel, weaned SD rats were treated with low selenium for 4 weeks and then T-2 toxin for 4 weeks. Knee cartilage was collected to harvest chondrocytes for gene expression profiling. Finally, the protein expression levels of CCNB1 and CCNG1 were verified in knee cartilage tissue of Kashin-Beck disease patients and normal controls by immunohistochemical staining. The systematic review found 52 cartilage disease-related cyclins and cyclin-dependent kinase genes, 23 of which were coexpressed in Kashin-Beck disease, including 15 upregulated and 8 downregulated genes. Under the intervention of a low selenium diet and T-2 toxin exposure, CCNB1 (FC = 0.36) and CCNG1 (FC = 0.73) showed a downward expression trend in rat articular cartilage. Furthermore, compared to normal controls, CCNB1 protein in Kashin-Beck disease articular cartilage was 71.98% and 66.27% downregulated in the superficial and middle zones, respectively, and 12.06% upregulated in the deep zone. CCNG1 protein was 45.66% downregulated in the superficial zone and 12.19% and 9.13% upregulated in the middle and deep zones, respectively. The differential expression of cyclins CCNB1 and CCNG1 may be related to articular cartilage damage in Kashin-Beck disease

The role of humic substances in drinking water in Kashin-Beck disease in China.

We conducted in vitro and in vivo assays in a selenium-deficient system to determine if organic matter (mainly fulvic acid; FA) is involved in a free radical mechanism of action for Kashin-Beck disease. Cartilage cell culture experiments indicated that the oxy or hydroxy functional groups in FA may interfere with the cell membrane and result in enhancement of lipid peroxidation. Experiments with rats demonstrated that toxicity from FA was reduced when the hydroxy group was blocked. Induction of lipid peroxidation by FA in liver and blood of rats was similar to that exhibited by acetyl phenyl hydrazine. FA accumulated in bone and cartilage, where selenium rarely concentrates. In addition, selenium supplementation in rats' drinking water inhibited the generation of oxy-free radicals in bone. We hypothesized that FA in drinking water is an etiological factor of Kashin-Beck disease and that the mechanism of action involves the oxy and hydroxy groups in FA for the generation of free radicals. Selenium was confirmed to be a preventive factor for Kashin-Beck disease

An in vitro model to study cartilage metabolism in Kashin-Beck disease

Kashin-Beck disease is endemic chronic degenerative osteoarthropathy whose main pathological changes occur in the growth plate and articular cartilage of human limbs and joints, where it is manifest as cartilage degeneration and necrosis. The effects of the disease on the growth plate therefore alter growth in children and can lead to growth arrest (short stature and limbs) and developmental deformities (crooked joints). In adulthood patients present with pain and deformity commonly affecting the hand, wrist, elbow, knee and ankle with radiological features and joint pattern involvement similar to those seen in rheumatoid arthritis. Past and current research suggests that Kashin-Beck disease, with its endemic geographical distribution in China and Tibet, is due to the combined presence of fungal mycotoxins (found on the stored food ingested by affected populations) and a regional selenium deficiency in the environment providing local food sources. This evidence is supported by the correlation between the geographical occurrence of these 2 factors and the incidence of Kashin-Beck disease. The objective of this study was to develop and in vitro cartilage culture system to mimic the changes seen in Kashin-Beck disease and thus determine the effects different sources of selenium, in the presence or absence of Nivalenol, had on cartilage neograft metabolism. Our hypothesis was that growth and metabolism of cartilage will be affected by exposure to either selenium or the mycotoxin Nivalenol or both in combination and these effects will mimic those found in Kashin-Beck disease. Collectively, the results of this study suggest that Nivalenol is the major contributor to cartilage pathology in this in vitro system that mimics Kashin-Beck disease, and that these deleterious effects are largely independent from selenium supplementation

DNA regulatory motif selection based on support vector machine (SVM) and its application in microarray experiment of Kashin-Beck disease

Conserved DNA sequences are essential to investigate the regulation and expression of nearby genes. The conserved regions can interact with certain proteins and can potentially determine the transcription speed and amount of the corresponding mRNA in gene replication process. In this paper, motifs of coexpressed genes of microarray experiments were explored with discovery algorithms. Then a selection algorithm based on support vector machine (SVM) was applied to identify those motifs which mostly influenced gene expression. This method combined the advantages from both matrix based motif finding and functional motif selection. When applied to Kashin-Beck disease (KBD), this method identified 9 motifs, and revealed that some motifs may be related to the immune reactions. In addition, we suggested that the methods used could be applied to other microarray experiments to explore the underlying relationships between motif types and gene functions.Key words: Support vector machine (SVM), microarray, motif discovery, gene regulation, Kashin-Beck disease

Kashin Beck Disease: more than just osteoarthrosis

The purpose of this study was to investigate the influence of body function, activities and pain on the level of activity in adults with Kashin Beck Disease (KBD). Seventy-five KBD patients with a mean age of 54.8 years (SD 11.3) participated. Anthropometrics, range of joint motion (ROM) and muscle strength were measured as well as the time-up-and-go test and functional tests for the lower and upper extremities. Activity was assessed with the participation scale and the WHO DAS II. In the shoulder, elbow, hip and knee joints, a severe decrease in ROM and bilateral pain was noted. A decrease in muscle strength was observed in almost all muscles. The timed-up-and-go test scores decreased. No or mild restriction in activity was found in 35%, and 33% experienced a moderate restriction whereas 32% had severe to extreme restriction. Activities in the lower extremities were mildly to moderately correlated to ROM and muscle strength, whereas in the upper extremities activities were correlated to range of joint motion. Activity was significantly associated with ROM after correction for muscle strength, gender and age. Participation was borderline significantly associated with ROM after correction for muscle strength, gender, age and the activity time-up-and-go. In KBD adults, a severe decrease in activity is primarily caused by decrease in ROM. These findings have strong influence on rehabilitation and surgical interventio

Osteo-Chondroprogenitor–Specific Deletion of the Selenocysteine tRNA Gene, Trsp, Leads to Chondronecrosis and Abnormal Skeletal Development: A Putative Model for Kashin-Beck Disease

Kashin-Beck disease, a syndrome characterized by short stature, skeletal deformities, and arthropathy of multiple joints, is highly prevalent in specific regions of Asia. The disease has been postulated to result from a combination of different environmental factors, including contamination of barley by mold mycotoxins, iodine deficiency, presence of humic substances in drinking water, and, importantly, deficiency of selenium. This multifunctional trace element, in the form of selenocysteine, is essential for normal selenoprotein function, including attenuation of excessive oxidative stress, and for the control of redox-sensitive molecules involved in cell growth and differentiation. To investigate the effects of skeletal selenoprotein deficiency, a Cre recombinase transgenic mouse line was used to trigger Trsp gene deletions in osteo-chondroprogenitors. Trsp encodes selenocysteine tRNA[Ser]Sec, required for the incorporation of selenocysteine residues into selenoproteins. The mutant mice exhibited growth retardation, epiphyseal growth plate abnormalities, and delayed skeletal ossification, as well as marked chondronecrosis of articular, auricular, and tracheal cartilages. Phenotypically, the mice thus replicated a number of the pathological features of Kashin-Beck disease, supporting the notion that selenium deficiency is important to the development of this syndrome

Recent advances in the research of an endemic osteochondropathy in China: Kashin-Beck disease

SummaryKashin-Beck disease (KBD) is an endemic chronic osteochondral disease, which has a high prevalence and morbidity in the Eastern Siberia of Russia, and in the broad diagonal, northern-east to southern-west belt in China and North Korea. In 1990's, it was estimated that in China 1–3 million people had some degree of symptoms of the disease, although even higher estimates have been presented. In China, the extensive prevalence peaked in the late 1950's, but since then, in contrast to the global trend of the osteoarthritis (OA), the number of cases has been dramatically falling. Up to 2013, there are 0.64 millions patients with the KBD and 1.16 millions at risk in 377 counties of 13 provinces or autonomous regions. This is obviously thanks to the preventive efforts carried out, which include providing millions of people with dietary supplements and clean water, as well as relocation of whole villages in China. However, relatively little is known about the molecular mechanisms behind the cartilage damage, the genetic and the environmental risk factors, and the rationale of the preventive effects. During the last decade, new data on a cellular and molecular level has begun to accumulate, which hopefully will uncover the grounds of the disease

Radiographic features of hand osteoarthritis in adult Kashin-Beck Disease (KBD): the Yongshou KBD study

Kashin-Beck disease (KBD) is a rare and severe osteoarthropathy endemic to China. We evaluated the frequency and patterns of hand radiographic osteoarthritis (rOA) in adults with and without KBD

The arthropathic and functional impairment features of adult Kashin-Beck disease patients in Aba Tibetan area in China

SummaryObjectThe purpose of the study was to analyze the features of arthropathic changes and functional impairments as well as the correlations between them for adult patients suffered with Kashin-Beck disease (KBD) in Aba Tibetan area of Sichuan Province, China.MethodNine hundred and eighty-nine adult KBD patients in Aba KBD prevalence area were investigated. The arthropathic changes including arthritic pain (evaluated by visual analog pain score (VAS)), deformity, limited range of joint motion (ROM), as well as daily living and working function were examined, evaluated and analyzed.ResultsNinety-two percent of patients suffered with multiple affected joints in both upper and lower extremities. The most frequently affected joints were knee (86.1%) and hand (77.2%). The most painful joints were knee (VAS 7.1 ± 1.9) and elbow (VAS 6.8 ± 2.1). Joint deformities most frequently represented as enlargement of interphalangeal joints (93.2%). Limitation of ROM occurred most frequently in hand (76.7%) and elbow (38.4%). Multiple linear regression analysis revealed that only joint pain (regression coefficient: −0.504, 95% confidence interval (CI): −0.820–0.188, P ＜ 0.001) and ROM (regression coefficient: 0.017, 95% CI: 0.011–0.024, P ＜ 0.001) were independent risk factors affecting daily living and working function.ConclusionMost adult patients suffered with multiple affected joints in both upper and lower limbs. The elbow, hand and knee were the most frequently and severely affected joints. The pain and limited ROM were the independent risk factors of daily living and working function

Research Progress of Drinking Water and Trace Elements in KBD Area

Kaschin-beck disease (KBD) is an endemic, chronic, and deformable osteochondral disease characterized by multiple degenerations and deep cell necrosis of epiphysis, epiphysis, and articular cartilage. The disease mainly affects children and adolescents aged 5-15, is concentrated in northeast and southwest China, involving 15 provinces, and extends into southeastern Siberia and North Korea. Although the etiology and pathogenesis of KBD are still not very clear, in recent years, more breakthroughs have been made in the supplement and update of its biogeochemical theory, especially in the analysis of hydrochemical characteristics and the study of the role of selenium and iodine in the pathogenic factors of KBD. Therefore, the present research results on the environmental geographical factors of Kashin-beck disease are reviewed in this paper