Downregulated SOX9 mediated by miR‑206 promoted cell apoptosis in Legg-Calvï¿½-Perthes disease

Luo, Junzhong; Han, Jiu-Hui; Li, Yazhou; Liu, Yuchang

doi:10.3892/ol.2017.7373

Cited by 9 publications

(10 citation statements)

References 21 publications

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“…This study also identified a significant downregulation of miR-217 in post-cryptorchidopexy testicular tissue. Similarly, miR-206 was significantly upregulated in post-cryptorchidopexy testicular tissue and was shown to promoted cell apoptosis in Legg–Calvé–Perthes disease [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Altered miRNA profile in testis of post-cryptorchidopexy patients with non-obstructive azoospermia

Tang

Huang

et al. 2018

Reprod Biol Endocrinol

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BackgroundCryptorchidism is one of the most common causes of non-obstructive azoospermia (NOA) leading to male infertility. Despite various medical approaches been utilised, many patients still suffer from infertility. MicroRNAs (miRNAs) play vital roles in the progress of spermatogenesis; however, little is known about the miRNA expression profile in the testes. Therefore, the miRNA profile was assessed in the testis of post-cryptorchidopexy patients.MethodsThree post-cryptorchidopexy testicular tissue samples from patients aged 23, 26 and 28 years old and three testis tissues from patients with obstructive azoospermia (controls) aged 24, 25 and 36 years old were used in this study. Next-generation sequencing (NGS) was used to perform the miRNA expression profiling. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) assays were subsequently used to confirm the results of several randomly-selected and annotated miRNAs.ResultsA series of miRNAs were found to be altered between post-cryptorchidopexy testicular tissues and control tissues, including 297 downregulated and 152 upregulated miRNAs. In the subsequent qRT-PCR assays, the expression levels of most of the selected miRNAs (9/12, P < 0.05) were consistent with the results of NGS technology. Furthermore, signal transduction, adaptive immune response and biological regulation were associated with the putative target genes of the differentially-expressed miRNAs via GO analysis. In addition, oxidative phosphorylation, Parkinson’s disease and ribosomal pathways were shown to be enriched using KEGG pathway analysis of the differentially-expressed genes.ConclusionsThis study provides a global view of the miRNAs involved in post-cryptorchidopexy testicular tissues as well as the altered expression of miRNAs compared to control tissues, thus confirming the vital role of miRNAs in cryptorchidism.Electronic supplementary materialThe online version of this article (10.1186/s12958-018-0393-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Altered miRNA profile in testis of post-cryptorchidopexy patients with non-obstructive azoospermia

Tang

Huang

et al. 2018

Reprod Biol Endocrinol

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“…In addition, several human studies revealed a genetic association of LCPD in a regional population with COL2A1gene mutations 25e27 , encoding type II collagen which is abundantly expressed by chondrocytes. MicroRNA may control to promote apoptosis in chondrocytes from LCPD patients 28 . Therefore, several lines of evidence suggest that chondrocytes play an important role in the pathogenesis of LCPD in human.…”

Section: Il6 Increase In the Epiphyseal Articular Cartilage Followingmentioning

confidence: 99%

“…It is interesting that human chondrocytes respond to tocilizumab by upregulating the cartilage anabolic marker Sox9 in vivo and vitro. Intriguingly, cell apoptosis is promoted in primary chondrocytes from LCPD patients due to downregulation of Sox9 by microRNA 28 . Furthermore, cell viability and migration is promoted by upregulation of Sox9 in chondrocytes 34 .…”

Section: An Anabolic Effect Of Tocilizumab On the Cartilage Matrix Wimentioning

confidence: 99%

IL6 receptor blockade preserves articular cartilage and increases bone volume following ischemic osteonecrosis in immature mice

Kamiya

Kuroyanagi

Aruwajoye

et al. 2019

Osteoarthritis and Cartilage

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Keywords:Juvenile ischemic osteonecrosis IL6 Tocilizumab Cartilage anabolism Legg-calve-perthes disease Bone formation s u m m a r y Objective: Juvenile ischemic osteonecrosis (JIO) of the femoral head is one of the most serious hip disorders causing a permanent deformity of the femoral head in childhood. We recently reported that interleukin 6 (IL6) is predominantly increased in the hip synovial fluid of patients with JIO and that articular chondrocytes are primary source of IL6. This study investigated whether an inhibition of IL6 receptor improves cartilage preservation and bone healing in JIO. Method: A small animal model (i.e., 6-week-old mouse) of JIO was treated with either saline or tocilizumab, an IL6 receptor blocker, for 6 weeks. Results: TUNEL-positive chondrocytes in the articular cartilage were reduced by the tocilizumab treatment, concomitant with the increase in cartilage matrix. The levels of a cartilage anabolic marker Sox9 was significantly increased in the articular cartilage of mice treated with tocilizumab. Micro-CT assessment showed tocilizumab treatment significantly increased trabecular epiphyseal bone volume (P ¼ 0.001, n ¼ 10), thickness (P ¼ 0.007) and number (P ¼ 0.014) and decreased bone separation (P ¼ 0.002) and its deformity (P ¼ 0.003). A bone formation marker, BMP2, and an angiogenic marker, vascular endothelial growth factor (VEGF), were both significantly increased by tocilizumab treatment under hypoxia using human chondrocytes while the bone resorption marker, RANKL/OPG ratio, was reduced. Conclusion: Tocilizumab treatment following ischemic osteonecrosis has cartilage anabolic effect and increases bone volume in JIO mouse model. The findings lead to a possible application of tocilizumab for preclinical study using a large animal model of JIO and a clinical trial to validate this treatment.

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“…it has been reported that mirnas serve important roles in chondrogenesis and lcPd. luo et al (16) revealed that mir-206 promoted cell apoptosis in lcPd via downregulation of SrY-box 9. Furthermore, it was demonstrated that overexpression of mir-214 in vitro and in vivo negatively regulated chondrocyte differentiation, possibly by targeting activating transcription factor 4 (aTF4) (17).…”

Section: Introductionmentioning

confidence: 99%

The role and underlying mechanisms of microRNA‑214 in Legg‑Calv�‑Perthes disease

Zhu

Liu

et al. 2019

Mol Med Report

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legg-calvé-Perthes disease (lcPd) is a pediatric form of femoral head osteonecrosis with unknown etiology. Micrornas (mirs) have been revealed to serve an important role in lcPd. Mir-214 serves an important role in chondrogenesis. The aim of the present study was to investigate the potential role of mir-214 in lcPd and the underlying mechanisms. The expression levels of mir-214 and B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax) in dexamethasone (deX)-treated Tc28 cells, and the femoral head cartilage tissues, serum and primary chondrocytes of patients with lcPd, and healthy individuals were determined via reverse transcription quantitative polymerase chain reaction and western blot analysis. a luciferase reporter assay was conducted to investigate the association between mir-214 and Bax, while cell viability was determined via an MTT assay, and flow cytometry was performed to investigate cell apoptosis. The results revealed that mir-214 was downregulated and Bax was upregulated in deX-treated Tc28 cells and tissues obtained from patients with lcPd. Mir-214 was demonstrated to directly target Bax and negatively regulate its expression. DEX administration significantly suppressed cell proliferation, promoted apoptosis and decreased the Bcl-2/Bax ratio in Tc28 cells; overexpression of mir-214 induced opposing effects, which were reversed by Bax overexpression. in conclusion, the results indicated that mir-214 and Bax may be potential therapeutic targets for the future clinical treatment of lcPd.

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Downregulated SOX9 mediated by miR‑206 promoted cell apoptosis in Legg-Calvï¿½-Perthes disease

Cited by 9 publications

References 21 publications

Altered miRNA profile in testis of post-cryptorchidopexy patients with non-obstructive azoospermia

Altered miRNA profile in testis of post-cryptorchidopexy patients with non-obstructive azoospermia

IL6 receptor blockade preserves articular cartilage and increases bone volume following ischemic osteonecrosis in immature mice

The role and underlying mechanisms of microRNA‑214 in Legg‑Calv�‑Perthes disease

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