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@#Objective To investigate the effect of aloperine(ALO)on interleukin-1β(IL-1β)-induced chondrocyte injury and its mechanism. Methods Chondrocytes were randomly divided into control(Con)group,IL-1 β group,IL-1β + ALO-L(25 mg/L)group,IL-1β + ALO-M(50 mg/L)group and IL-1 β + ALO-H(100 mg/L)group;Con group,IL-1βgroup,IL-1β + miR-NC group and IL-1β + miR-16-5p group;Con group,IL-1β group,IL-1β + si-NC group and IL-1β + siSOX5 group. Cells in IL-1β group were treated with 10 ng/mL IL-1β,while no treatment was given in Con group. The transcription levels of miR-16-5p and SOX5 mRNA in chondrocytes were detected by qRT-PCR;The contents of IL-6,TNF-αand IL-1β were detected by ELISA;The expression levels of Bcl-2,Bax and SOX5 protein were detected by Western blot and the apoptosis was detected by flow cytometry. Results Compared with IL-1 β group,the contents of IL-6,TNF-α and IL-1βin IL-1β + ALO-L group,IL-1β + ALO-M group and IL-1β + ALO-H group decreased significantly(t = 5. 002～20. 653,each P < 0. 001),the apoptosis rate decreased significantly(t = 5. 473～17. 371,each P < 0. 001),the expression level of Bcl-2 protein increased significantly(t = 7. 800～16. 100,each P < 0. 001),and the expression level of Bax protein decreased significantly(t = 4. 993～14. 311,each P < 0. 001);The mRNA transcription level of miR-16-5p gene increased significantly(t = 6. 688～16. 545,each P < 0. 001),while the mRNA transcription level and protein expression level of SOX5 gene decreased significantly(t = 4. 609～15. 393,each P < 0. 001). Compared with the IL-1β + miR-NC group,the mRNA transcription level of miR-16-5p in the IL-1β + miR-16-5p group increased significantly(t = 17. 106,P < 0. 001),the contents of IL-6,TNF-α and IL-1 β decreased significantly(t = 15. 030～20. 013,each P < 0. 001),the apoptosis rate decreased significantly(t = 12. 273,P < 0. 001),the expression level of Bcl-2 protein increased significantly(t = 15. 652,P < 0. 001),and the expression level of Bax protein decreased significantly(t = 12. 999,P < 0. 001). Compared with IL-1β +si-NC group,the expression level of SOX5(t = 13. 444,P < 0. 001),IL-6,TNF-α and IL-1β in IL-1β + si-SOX5 group decreased significantly(t = 14. 087～17. 103,each P < 0. 001),the apoptosis rate decreased significantly(t = 11. 991,P < 0. 001),the expression level of Bcl-2 protein increased significantly(t = 13. 864,P < 0. 001),and the expression level of Bax protein decreased significantly(t = 11. 818,P < 0. 001). Conclusion Alo inhibited the apoptosis of chondrocytes induced by IL-1β,thus reducing the injury of chondrocytes,of which the mechanism might be regulating the expression of miR-16-5p and SOX5 and the secretion of inflammatory factors in chondrocytes.
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Objective To investigate the expression and clinical significance of transcription factor SOX5 in peripheral blood mononuclear cells (PBMCs) and serum in patients with rheumatoid arthritis (RA). Methods The relative expression of representative genes of the SOX gene family in the PBMCs from RA patients were detected by Real-Time Polymerase Chain Reaction (RT-PCR), and serum levels of SOX5 expression were measured by enzyme-linked immunosorbent assay (ELISA) in 30 RA patients, 27 osteoarthritis (OA) patients and 30 healthy controls (HC). The expression levels of SOX5 in PBMCs were detected by RT-PCR after stimulated with IL-6, TNF-α, IL-1β and IL-17 for 24 hours. The relationship between SOX5 and receptor activator of nuclear factor κB ligand (RANKL) was detected by co-Immunoprecipitation (co-IP). The formation of TRAP-positive cells after silence SOX5 in osteoclast precursor cell treated with RANKL was observed by Tartrate-resistant acid phasphate stain (TRAP). The differences were tested using one-way ANOVA followed by Student-Newman-Keuls post hoc analysis Correlations were analyzed using Pearson's analysis. Results SOX5 was predominantly expressed in the PBMCs of RA as compared with other SOX family genes in PBMC. PBMC levels of SOX5 in RA patients (21±19) were higher than the OA patients (10±8) and healthy control group (5±4)(F=8.343, P<0.01). While, Serum levels of SOX5 in RA patients [(19132±12054) pg/ml were higher than the OA patients [(9065±15172) pg/ml] and healthy control group [(3242±1251) pg/ml] (F=15.31, P<0.01). IL-6, TNF-α, IL-1β and IL-17 led to the up-regulation of SOX5 expression in PBMCs. IL-6, TNF-α, IL-1β promoted the interaction of SOX5 and RANKL in PBMCs. Silencing SOX5 reduced the formation of TRAP-positive cells in osteoclast precursor cell treated with RANKL. Conclusion Our results have proven that transcriptional factor SOX5 regulates the expression of RANKL and participates in the process of RA bone erosion. Inhibition of SOX5 expression may be a new therapy target of RA.
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Sox5 gene is located on 12p12.1 containing 29 exons.The gene can transcript 5 variants, thus produce 5 isoforms.L-SOX5A is an isoform with multiple functions , include regulate embryonic development , and determine cell differentiation .Sox5 also plays a role in pathogenesis of prostate cancer , breast cancer and lymphoma .
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AIM: To investigate the differences in the distribution of SRY-related HMG box 5 (SOX5) gene single nucleotide polymorphisms (SNPs) among stable chronic obstructive pulmonary disease (COPD) patients, COPD with pulmonary hypertension (PH) patients and healthy controls, and to explore the association of the SOX5 SNPs in COPD-related PH.METHODS: From April 2013 to April 2015, 250 patients with stable COPD were enrolled continuous-ly in Ningxia People’s Hospital according to COPD treatment guidelines (2013 edition).All the patients received echocar-diography, and were divided into COPD with PH group [pulmonary artery systolic pressure (PASP)≥50 mmHg, n =103] and COPD without PH group (PASP loci was performed using MassARRAY genotyping system ( Sequenom).Genotype frequencies were calculated.RE-SULTS: Age, sex and smoking index showed no significantly difference between control group and COPD group, neither between COPD with PH group and COPD without PH group.Genotype frequencies of SOX5 gene rs10842262 and rs11046966 loci between control group and COPD group was of significant difference (P<0.05).Genotype frequencies of SOX5 gene rs10842262 and rs11046966 loci showed no significant difference between COPD with PH group and COPD without PH group.CONCLUSION: SOX5 gene rs10842262 and rs11046966 loci may play an important role in COPD, but not in COPD-related PH.
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SoxD transcription factor subfamily includes three members, Sox5, Sox6, and Sox13. Like other Sox genes, they contain the High-Mobility-Group (HMG) box as the DNA binding domain but in addition feature the subgroup-specific leucine zipper motif. SoxD genes are expressed in diverse cell types in multiple organs during embryogenesis and in adulthood. Among the cells expressing them are those present in the developing nervous system including neural stem (or progenitor) cells as well as differentiating neurons and oligodendrocytes. SoxD transcription factors do not contain distinct activator or repressor domain, and they are believed to function in modulation of other transcription factors in promoter- specific manners. This brief review article will attempt to summarize the latest studies on the function of SoxD genes in embryogenesis with a particular emphasis on the regulation of neural development.