Dysregulation of Transcription Profile of Selenoprotein in Patients with Kashin-Beck Disease and Its Effect on Se Deficiency–Induced Chondrocyte Apoptosis

Objective miR-146a-5p was found to be significantly upregulated in cartilage tissue of patients with osteoarthritis (OA). NUMB was shown to be involved in the autophagy regulation process of cells. We aimed to learn whether NUMB was involved in the apoptosis or autophagy process of chondrocytes in OA and related with miR-146a-5p. Methods QRT-PCR was used to detect miR-146a-5p level in 22 OA cartilage tissues and 22 controls. The targets of miR-146a-5p were analyzed using software and the luciferase reporter experiment. The apoptosis and autophagy, and related proteins were detected in chondrocytes treated with miR-146a-5p mimic/inhibitor or pcDNA3.1-NUMB/si-NUMB and IL-1β, respectively. In vivo experiment, intra-articular injection of miR-146a-5p antagomir/NC was administered at the knee of OA male mice before and after model construction. Chondrocyte apoptosis and the expression of apoptosis and autophagy-related proteins were also detected. Results miR-146a-5p was highly expressed in knee cartilage tissue of patients with OA, while NUMB was lowly expressed and negatively regulated by miR-146a-5p. Upregulation of miR-146a-5p can promote cell apoptosis and reduce autophagy of human and mouse chondrocytes by modulating the levels of cleaved caspase-3, cleaved PARP, Bax, Beclin 1, ATG5, p62, LC3-I, and LC3-II. Increasing the low level of NUMB reversed the effects of miR-146a-5p on chondrocyte apoptosis and autophagy. Intra-articular injection of miR-146a-5p antagomir can also reverse the effects of miR-146a-5p on the apoptosis and autophagy of knee joint chondrocytes in OA mice. Conclusion Downregulation of miR-146a-5p suppresses the apoptosis and promotes autophagy of chondrocytes by targeting NUMB in vivo and in vitro.

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Kashin-Beck Disease Diagnosis Based on Deep Learning from Hand X-ray Images

Computer Methods and Programs in Biomedicine ◽

10.1016/j.cmpb.2020.105919 ◽

2020 ◽

pp. 105919

Author(s):

Jinyuan Dang ◽

Hu Li ◽

Kai Niu ◽

Zhiyuan Xu ◽

Jianhao Lin ◽

...

Keyword(s):

Deep Learning ◽

Disease Diagnosis ◽

X Ray ◽

Beck Disease

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Selenium deficiency induces spleen pathological changes in pigs by decreasing selenoprotein expression, evoking oxidative stress, and activating inflammation and apoptosis

Journal of Animal Science and Biotechnology ◽

10.1186/s40104-021-00587-x ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Shuang Li ◽

Wenjuan Sun ◽

Kai Zhang ◽

Jiawei Zhu ◽

Xueting Jia ◽

...

Keyword(s):

Oxidative Stress ◽

Inflammatory Cytokines ◽

The Body ◽

Terminal Deoxynucleotidyl Transferase ◽

Antioxidant Systems ◽

Tunel Staining ◽

White Pulp ◽

Sibling Pairs ◽

Se Deficiency ◽

Spleen Index

Abstract Background The immune system is one aspect of health that is affected by dietary selenium (Se) levels and selenoprotein expression. Spleen is an important immune organ of the body, which is directly involved in cellular immunity. However, there are limited reports on Se levels and spleen health. Therefore, this study established a Se-deficient pig model to investigate the mechanism of Se deficiency-induced splenic pathogenesis. Methods Twenty-four pure line castrated male Yorkshire pigs (45 days old, 12.50 ± 1.32 kg, 12 full-sibling pairs) were divided into two equal groups and fed Se-deficient diet (0.007 mg Se/kg) or Se-adequate diet (0.3 mg Se/kg) for 16 weeks. At the end of the trial, blood and spleen were collected to assay for erythroid parameters, the osmotic fragility of erythrocytes, the spleen index, histology, terminal deoxynucleotidyl transferase nick-end labeling (TUNEL) staining, Se concentrations, the selenogenome, redox status, and signaling related inflammation and apoptosis. Results Dietary Se deficiency decreased the erythroid parameters and increased the number of osmotically fragile erythrocytes (P < 0.05). The spleen index did not change, but hematoxylin and eosin and TUNEL staining indicated that the white pulp decreased, the red pulp increased, and splenocyte apoptosis occurred in the Se deficient group. Se deficiency decreased the Se concentration and selenoprotein expression in the spleen (P < 0.05), blocked the glutathione and thioredoxin antioxidant systems, and led to redox imbalance. Se deficiency activated the NF-κB and HIF-1α transcription factors, thus increasing pro-inflammatory cytokines (IL-1β, IL-6, IL-8, IL-17, and TNF-α), decreasing anti-inflammatory cytokines (IL-10, IL-13, and TGF-β) and increasing expression of the downstream genes COX-2 and iNOS (P < 0.05), which in turn induced inflammation. In addition, Se-deficiency induced apoptosis through the mitochondrial pathway, upregulated apoptotic genes (Caspase3, Caspase8, and Bak), and downregulated antiapoptotic genes (Bcl-2) (P < 0.05) at the mRNA level, thus verifying the results of TUNEL staining. Conclusions These results indicated that Se deficiency induces spleen injury through the regulation of selenoproteins, oxidative stress, inflammation and apoptosis.

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Arthroscopic Ankle Arthrodesis for Treating Osteoarthritis in a Patient with Kashin-Beck Disease

Case Reports in Medicine ◽

10.1155/2014/931278 ◽

2014 ◽

Vol 2014 ◽

pp. 1-5 ◽

Cited By ~ 1

Author(s):

Kenjiro Iwasa ◽

Noriyuki Kanzaki ◽

Takaaki Fujishiro ◽

Shinya Hayashi ◽

Shingo Hashimoto ◽

...

Keyword(s):

Humic Acid ◽

Growth Plate ◽

Preventive Treatment ◽

Ankle Arthrodesis ◽

Ankle Osteoarthritis ◽

Pathologic Feature ◽

Skeletal Deformity ◽

Degenerative Osteoarthritis ◽

Beck Disease

Kashin-Beck disease (KBD) is an endemic degenerative osteoarthritis. Death of cartilage and growth plate is the pathologic feature; therefore, KBD involves skeletal deformity and often results in osteoarthritis. Deficiency of selenium, high humic acid levels in water, and fungi on storage gains are considered the cause of KBD. The most frequently involved joints are ankles, knees, wrists, and elbows and symptoms are pain and limited motions of those joints. The main treatments for KBD are rehabilitation and osteotomy to correct the deformities because preventive treatment has not been established. In this report, we present a case of ankle osteoarthritis due to KBD and first describe arthroscopic ankle arthrodesis for treating osteoarthritis of KBD.

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