SFMBT2 positively regulates SOX9 and chondrocyte proliferation

Hussain, Saddam; Sun, Mengyao; Guo, Yue; Mushtaq, Nosheen; Zhao, Yitong; Yuan, Ying; Hussain, N.; Osoro, Ezra Kombo; Suleiman, Abubakar; Sadiq, Muhammad; Zhang, Fujun; Han, Yong; Sun, Jian; Lu, Shemin

doi:10.3892/ijmm.2018.3894

Cited by 9 publications

(9 citation statements)

References 61 publications

(63 reference statements)

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“…SOX9 is a master transcription factor that is essential for chondrogenic differentiation and development from MSCs [57]. Its expression is high in mitotic and early prehypertrophic chondrocytes, but downregulated in hypertrophic chondrocytes [42,58]. In this study, we confirmed that during the 21-day chondrogenic differentiation, SOX9 expression was significantly upregulated at day 7 and was maintained at a high level, with an expression pattern similar to that of COL2.…”

Section: Discussionsupporting

confidence: 77%

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MicroRNA-27b targets CBFB to inhibit differentiation of human bone marrow mesenchymal stem cells into hypertrophic chondrocytes

Liu

Chen

et al. 2020

Stem Cell Res Ther

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Background Human bone marrow-derived mesenchymal stem cells (hBMSCs) have chondrocyte differentiation potential and are considered to be a cell source for cell-transplantation-mediated repair of cartilage defects, including those associated with osteoarthritis (OA). However, chondrocyte hypertrophic differentiation is a major obstacle for the application of hBMSCs in articular cartilage defect treatment. We have previously shown that microRNA-27b (miR-27b) inhibits hypertrophy of chondrocytes from rat knee cartilage. In this study, we investigated the role of miR-27b in chondrocyte hypertrophic differentiation of hBMSCs. Methods Chondrogenic marker and microRNA expression in hBMSC chondrogenic pellets were evaluated using RT-qPCR and immunohistochemistry. The hBMSCs were transfected with miR-27b before inducing differentiation. Gene and protein expression levels were analyzed using RT-qPCR and western blot. Coimmunoprecipitation was used to confirm interaction between CBFB and RUNX2. Luciferase reporter assays were used to demonstrate that CBFB is a miR-27b target. Chondrogenic differentiation was evaluated in hBMSCs treated with shRNA targeting CBFB. Chondrogenic hBMSC pellets overexpressing miR-27b were implanted into cartilage lesions in model rats; therapeutic effects were assessed based on histology and immunohistochemistry. Results The hBMSCs showed typical MSC differentiation potentials. During chondrogenic differentiation, collagen 2 and 10 (COL2 and COL10), SOX9, and RUNX2 expression was upregulated. Expression of miR-140, miR-143, and miR-181a increased over time, whereas miR-27b and miR-221 were downregulated. Cartilage derived from hBMSC and overexpressing miR-27b exhibited higher expression of COL2 and SOX9, but lower expression of COL10, RUNX2, and CBFB than did the control cartilage. CBFB and RUNX2 formed a complex, and CBFB was identified as a novel miR-27b target. CBFB knockdown by shRNA during hBMSC chondrogenic differentiation led to significantly increased COL2 and SOX9 expression and decreased COL10 expression. Finally, miR-27b-overexpressing hBMSC chondrogenic pellets had better hyaline cartilage morphology and reduced expression of hypertrophic markers and tend to increase repair efficacy in vivo. Conclusion MiR-27b plays an important role in preventing hypertrophic chondrogenesis of hBMSCs by targeting CBFB and is essential for maintaining a hyaline cartilage state. This study provides new insights into the mechanism of hBMSC chondrocyte differentiation and will aid in the development of strategies for treating cartilage injury based on hBMSC transplantation.

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Section: Discussionsupporting

confidence: 77%

“…SOX9 is a negative regulator of chondrocyte hypertrophic differentiation [42], and the β-catenin pathway is involved in controlling SOX9 expression [43]. Thus, we examined whether miR-27b enhanced SOX9 expression through the β-catenin pathway.…”

Section: Mir-27b Inhibits Hbmsc Hypertrophic Chondrocyte Differentiatmentioning

confidence: 99%

MicroRNA-27b targets CBFB to inhibit differentiation of human bone marrow mesenchymal stem cells into hypertrophic chondrocytes

Liu

Chen

et al. 2020

Stem Cell Res Ther

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“…As a result, the survival of chondrocytes and their phenotypic stability and anabolic/catabolic balance activity are important for the maintenance of articular cartilage [27]. We further analyzed the changes of chondrocyte gene expression under the action of oligostilbenes, including matrix metalloproteinase 13(MMP13), an enzyme that is involved in the degradation of extracellular matrix (ECM) in OA [28]; COL2A1, the gene that provides type II collagen, which is the main protein in ECM of chondrocytes [29]; SOX9, an important factor in promoting cartilage differentiation, and its expression is decreased in OA patients [30]. We found that they all have the ability to inhibit the ECM degradation of chondrocytes and promote the expression of chondrocyte-specific genes.…”

Section: Discussionmentioning

confidence: 99%

Protective effects of ten oligostilbenes from Paeonia suffruticosa seeds on interleukin-1β-induced rabbit osteoarthritis chondrocytes

Cen

Liu

et al. 2019

BMC Chemistry

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Background: Paeonia suffruticosa is an important traditional Chinese herb used to treat osteoarthritis (OA) and oligostilbenes are the main active ingredient of the seeds of P. suffruticosa. The monomer trans-resveratrol of this species was demonstrated to have chondroprotective effects as a lead compound for the treatment of osteoarthritis, but it has not been applied due to its low efficacy. Methods: Oligostilbenes were isolated by chromatography and were identified by NMR and HPLC. A rabbit osteoarthritis chondrocyte model was induced by interleukin-1β and was treated with individual drugs to systematically evaluate their effects. Cell Counting Kit 8 was used to test their effects on cell viability, calculate EC 50 and plot a doseresponse curve.Their effects on apoptosis were analyzed by Annexin V and PI staining, and the expression of chondrocyte-specific genes COL2A1, MMP13 and SOX9 was evaluated by real-time PCR. Results: Paeonia suffruticosa seed extract could promote the cell viability of rabbit OA chondrocytes at low concentration and then ten oligostilbenes were isolated from it. Trans-oligostilbenes were better than their cis-forms, trimers and dimers were better than monomers for promoting the cell viability of rabbit osteoarthritis chondrocytes. None of the oligostilbenes was more effective than seed extract at the appropriate concentration; 1 μM oligostilbenes all showed various anti-apoptotic effects. Trans-gnetin H showed the best effect on proliferation and inhibition of MMP13 expression on OA chondrocytes, while trans-viniferin was most effective in promoting the expression of COL2A1 and SOX9. Conclusions: Ten oligostilbenes from P. suffruticosa seed all have certain protective effects on OA chondrocytes at low concentration. The trans-viniferin and some trimers have the potential to be further developed for the treatment of osteoarthritis because they were more effective than resveratrol and diacerein. The synergistic effect that may exist between oligostilbenes also warrants further research.

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“…Pro‐inflammatory cytokines, such as IL‐1β and TNF‐α, contribute to a complex network of biochemical factors in chondrocytes to allot anabolism and catabolism (Fernandes et al., 2002). Sox9 and its downstream target Col2a1 are the master regulators to resist OA‐like changes (Hussain et al., 2018). Our results showed that TNF‐α combined with IL‐1β‐induced the down‐regulation of Sox9 and Col2a1 mRNA expression were reinforced in punicalin‐treated chondrocytes (Figure 4a,b).…”

Section: Resultsmentioning

confidence: 99%

Punicalin alleviates TNF‐α‐ and IL‐1β‐induced chondrocyte dysfunction and cartilage metabolism via mediating FOXO3 signaling axis

et al. 2021

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Forkhead box O3 (FOXO3) transcription factor is involved in chondral homeostasis of normal, aging and osteoarthritis (OA) cartilage. At present, we aimed to investigate whether FOXO3 is a target of punicalin to prevent IL‐1β‐ and TNF‐α‐induced chondrocyte dysfunction in vitro and in vivo models. Cell and mouse models of chondrocyte dysfunction were established to determine the pharmacological value of hydrolyzable tannin, punicalin, which was extracted from the pomegranate. FOXO3 protein levels in the nucleus and cytoplasm were analysed using western blot. Safranine O staining was performed to evaluate the expansion of growth plate and chondrocyte differentiation in IL‐1β‐ and TNF‐α‐treated mice. In IL‐1β‐ and TNF‐α‐treated chondrocytes and mice, IL‐1β and TNF‐α evoked phosphorylation and nucleocytoplasmic shuttling of FOXO3, as well as reduced FOXO3 expression levels in the nucleus. However, punicalin treatment repressed FOXO3 phosphorylation and cytoplasmic transfer. Punicalin treatment improved IL‐1β and TNF‐α‐induced growth inhibition and apoptosis of chondrocyte and the abnormal expansion of growth plate and hypertrophic zone. Moreover, punicalin could maintain the normal phenotype of chondrocyte via mediating multiple gene expression. Punicalin showed a beneficial effect on IL‐1β‐ and TNF‐α‐stimulated chondrocytes and cartilaginous metabolic disorders via preserving the transcriptional activity of FOXO3. Practical applications Our study presents a prospective adjuvant therapeutic drug, punicalin, to prevent inflammation‐related cartilage injury and chondrocyte dysfunction.

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SFMBT2 positively regulates SOX9 and chondrocyte proliferation

Cited by 9 publications

References 61 publications

MicroRNA-27b targets CBFB to inhibit differentiation of human bone marrow mesenchymal stem cells into hypertrophic chondrocytes

MicroRNA-27b targets CBFB to inhibit differentiation of human bone marrow mesenchymal stem cells into hypertrophic chondrocytes

Protective effects of ten oligostilbenes from Paeonia suffruticosa seeds on interleukin-1β-induced rabbit osteoarthritis chondrocytes

Punicalin alleviates TNF‐α‐ and IL‐1β‐induced chondrocyte dysfunction and cartilage metabolism via mediating FOXO3 signaling axis

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