EUROPEAN JOURNAL OF PHARMACOLOGY
·
2024
·
IF 4.2
Yuqian Chen,Jin Liu,Qianqian Zhang,Limin Chai,Huan Chen,Danyang Li,Yan Wang,Yuanjie Qiu,Nirui Shen,Jia Zhang,Qingting Wang,Jian Wang,Xinming Xie,Shaojun Li,Manxiang Li
Stromal derived factor 1 (SDF1) has been shown to be involved in the pathogenesis of pulmonary artery hypertension (PAH). However, the detailed molecular mechanisms remain unclear. To address this, we utilized primary cultured rat pulmonary artery smooth muscle cells (PASMCs) and monocrotaline (MCT)-induced PAH rat models to investigate the mechanisms of SDF1 driving PASMCs proliferation and pulmonary arterial remodeling. SDF1 increased runt-related transcription factor 2 (Runx2) acetylation by Calmodulin (CaM)-dependent protein kinase II (CaMKII)-dependent HDAC4 cytoplasmic translocation, elevation of Runx2 acetylation conferred its resistance to proteasome-mediated degradation. The accumulation of Runx2 further upregulated osteopontin (OPN) expression, finally leading to PASMCs proliferation. Blocking SDF1, suppression of CaMKII, inhibition the nuclear export of HDAC4 or silencing Runx2 attenuated pulmonary arterial remodeling and prevented PAH development in MCT-induced PAH rat models. Our study provides novel sights for SDF1 induction of PASMCs proliferation and suggests that targeting SDF1/CaMKII/HDAC4/Runx2 axis has potential value in the management of PAH.
研究领域:
心血管疾病
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2016
·
IF 2.618
Xiaonan Zhang,Kang Chen,Bo Wei,Xingwang Liu,Zeming Lei,Xizhuang Bai
Glucocorticoid-induced osteoporosis (GIOP) is the primary cause of secondary osteoporosis and the existing therapeutic strategies are limited. The aim of this study is to evaluate the effects of ginsenosides (GS) Rg3 on dexamethasone (DEX)-induced osteoporosis in vivo and in vitro. GIOP rat was established by DEX injection for 5 weeks and treated by GS Rg3 10 or 20 mg/kg. Body weight and bone mineral density (BMD) of rats were measured at the beginning and the end of the experiment. Histological changes of femurs were observed using HE staining. The in vitro model was established on primary osteoblasts induced by DEX. CCK-8 assay was used to test the cell viability. Bone metabolism markers in serum or primary osteoblasts were detected using biochemical kits. Real time PCR and western blot were used to measure nuclear factor-kappa B ligand (RANKL), osteoprotegerin (OPG), bone morphogenic protein-2 (BMP-2), BMP receptor 1A (BMPR1A) and Runx2 expression. The results demonstrated that GS Rg3 prevented DEX-induced body weight and BMD reduction, enhanced secretion of bone formation markers and decreased bone resorption markers. In addition, GS Rg3 was found to prevent the suppression of BMP-2/BMPR1A/Runx2 signals induced by DEX both in GIOP rats and primary osteoblasts. Inhibition of BMP-2 by noggin completely blocked the bone-alkaline phosphatase-secretion-promoted effect of GS Rg3 in vitro. These data suggest that GS Rg3 attenuates GIOP through regulating BMP-2 signaling pathway. This study provides a potential drug candidate for GIOP therapy.
研究领域:
药理学
·
骨科
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2020
·Vol. 10
·期 1
·1-7
·
IF 3.998
Wang Xueni,Liao Xiuling,Zhang Yimin,Wei Linyao,Pang Yuzhou
Schisandrin B (SchB) is the highest content of biphenyl cyclooctene lignans in Schisandra chinensis . It has been reported to have a variety of pharmacological effects, including anti-inflammatory, anti-oxidant, anti-cancer, heart protection, liver protection. In this study, we found that SchB can promote the proliferation of MC3T3-E1 subclone 14 cells. Meanwhile, we found that SchB can regulate the BMP2-SMADs signaling pathway by increasing gene and protein expression of those relative biomolecules. Furthermore, SchB can raise the RUNX2 and SP7 expression in both mRNA and protein levels. Since the role of BMP2-SMADs-RUNX2-SP7 signaling axis in osteoblast proliferation and differentiation has been well documented. The present experimental findings indicate that SchB could promote the proliferation and differentiation of osteoblasts through BMP2-SMADs-RUNX2-SP7 signaling axis.
研究领域:
药理学
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细胞生物学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Nutrients
·
2022
·Vol. 14
·期 9
·1940
·
IF 6.706
Kuaitian Wang,Xiao Kong,Mengdi Du,Wei Yu,Zhenhua Wang,Bo Xu,Jianrong Yang,Jingru Xu,Zhili Liu,Yongqiang Cheng,Jing Gan
DEDEQIPSHPPR, the calcium-binding peptide (CBP) identified in soy yogurt, was proven to be a potential cofactor in osteoporosis prevention in our previous study, but the mechanism was unknown. In this study, the activity of alkaline phosphatase (ALP) and osteocalcin (OCN), the regulation of RUNX2, and the expression of TβRI were investigated to elucidate the underlying mechanism. The results show that CBP upregulated ALP activity and OCN concentration and increased the expression of RUNX2 and the activation of the MAPK signaling pathway. Similarly, the expression of osteogenesis-related genes in osteoblasts also increased upon CBP treatment. Moreover, the CBP-induced enhancement of ALP activity and phosphorylation levels in the p38 pathway was inhibited by treatment with a p38 inhibitor (SB203538) and TβRI inhibitor (SB431542), respectively, suggesting that p38 and TβRI were involved in the osteogenic action. Based on the signaling pathways, the intracellular calcium concentration was significantly elevated by CBP, which was correlated with the increased behavioral functions and the relative fluorescence intensity of the bone mass. These findings suggest that CBP stimulates osteoblast differentiation and bone mineralization through the activation of RUNX2 via mechanisms related to the TβRI-p38-MAPK signaling pathways, further highlighting CBP’s important potential for treating osteoporosis.Keywords:bone remodeling;soy peptide CBP;osteoblast;differentiation;p38-MAPK;RUNX2
研究领域:
生物学
·
生物化学
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药理学
·
骨骼生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Regenerative Medicine
·
2022
·
IF 3.21
Ming-Zhi Huang,Hong-Yan Chen,Guo-Xuan Peng,Hong Sun,Hong-Cheng Peng,Hai-Yang Li,Xiang-Hui Liu,Qing Li
Aim: Effect of artesunate (ART)-treated bone marrow-derived mesenchymal stem cells-derived exosomes (BMSC-Exos) on osteogenesis and its underlying mechanisms were investigated. Materials & methods: Proliferation, alkaline phosphatase activity and calcified nodule formation of osteoblasts were determined. A mouse model of osteoporosis was established by ovariectomy. Results:SNHG7 was upregulated in BMSC-Exos by twofold, which was further enhanced in ART-BMSC-Exos by about twofold. ART intensified BMSC-Exos-induced proliferation, alkaline phosphatase activity by about fourfold, calcified nodule formation by about threefold and upregulation of osteogenesis related molecules RUNX2 (by 50%), BMP2 (by 30%) and ATF4 (by 40%) via delivering SNHG7. Mechanistically, SNHG7 recruited TAF15 to facilitate RUNX2 stability. Conclusion: ART-BMSC-Exos facilitated osteogenesis via delivering SNHG7 by modulating TAF15/RUNX2 axis.Plain language summaryOsteoporosis is the most common and complex skeletal disorder worldwide. Exosomes derived from bone marrow-derived mesenchymal stem cells (BMSC-Exos) have been recognized as an ideal seed source for bone tissue regeneration. We aimed to explore the effect of artesunate (ART)-BMSC-Exos on osteogenesis and its underlying mechanisms. The results showed that ART-BMSC derived exosomal SNHG7 facilitated osteoblast activity and attenuated osteogenesis in mice by modulating TAF15/RUNX2 pathway. Our findings contribute to a better understanding of the therapeutic mechanisms of ART-BMSCs-Exos for osteoporosis and suggest ART-BMSC-Exos as a novel therapeutic option for osteoporosis.
研究领域:
干细胞生物学
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骨骼生物学
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分子生物学
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再生医学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Bioscience-Landmark
·
2023
·Vol. 28
·期 7
·139
·
IF 3.1
Yanan Zhang,Junjun Huang,Lingyan Yan,Rong Jia,Jihua Guo
Background: RUNX2 (Runt-related transcription factor 2) acts as a key regulator in the odontogenic differentiation of human dental pulp stem cells (hDPSCs). Moreover, the inclusion of exon 5 is important for RUNX2 function. Our previous study showed that Y-Box Binding Protein 1 (YBX1) promoted RUNX2 exon 5 inclusion and mineralization of hDPSCs. However, the regulatory mechanism of RUNX2 exon 5 alternative splicing needed further exploration. Methods: The expression level of heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) during the odontogenic differentiation of hDPSCs was analyzed by RT-PCR and Western blot. The roles of hnRNP A1 in the alternative splicing of RUNX2 exon 5 and the odontogenic differentiation of dental mesenchymal cells were analyzed by gain- and loss-of-function experiments. Results: Surprisingly, we found an alternative splicing factor, hnRNP A1, which had an opposite role to YBX1 in regulating RUNX2 exon 5 inclusion and odontogenic differentiation of hDPSCs. Through gain- and loss-of-function assay, we found that hnRNP A1 suppressed the inclusion of RUNX2 exon 5, resulting in the inhibition of odontoblastic differentiation. The overexpression of hnRNP A1 can inhibit the expression of ALP (alkaline phosphatase) and OCN (osteocalcin), and the formation of mineralized nodules during the odontogenic differentiation of both hDPSCs and mouse dental papilla cells (mDPCs), whereas the opposite results were obtained with an hnRNP A1 knockdown preparation. Conclusions: The present study indicated that hnRNP A1 suppressed RUNX2 exon 5 inclusion and reduced the odontogenic differentiation ability of hDPSCs and mDPCs.
研究领域:
分子生物学
·
干细胞研究
·
牙科学
·
转录调控
·
可变剪接
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioengineered
·
2021
·
IF 3.269
Xiaochen Wang,Yaochuan Mi,Wei He,Xiaona Hu,Shuo Yang,Lu Zhao,Yanyang Zhang,Binhong Wen
Diabetic osteoporosis (DOP) is a chronic complication of diabetes in the skeletal system. High level of miR-340-5p may be harmful to the bone formation. In this study, the DOP model of rats was successfully established via streptozotocin (STZ) and ovariectomy (OVX) treatment. It was manifested by reduced body weight, insulin level, alkaline phosphatase (ALP) activity, and osteocalcin (OCN) and collagen-I expressions, as well as increased concentration of fasting blood glucose. Moreover, we found that miR-340-5p expression was increased while runt-related transcription factor-2 (RUNX2) was decreased in femurs. Furthermore, the effects of miR-340-5p on osteogenic differentiation (OD) in high glucose (HG)-treated MC3T3-E1 cells were explored. Exposure to OD and HG contributed to elevated miR-340-5p level. Inhibition of miR-340-5p enhanced ALP level, calcium deposition, and OCN, collagen-I and RUNX2 levels. On the contrary, miR-340-5p overexpression reversed these promotional effects. Luciferase assay indicated that RUNX2 may be a target gene of miR-340-5p. Moreover, RUNX2 deficiency decreased miR-340-5p inhibition-induced ALP activity, calcium accumulation and OCN, collagen-I, RUNX2 levels. In short, the above findings revealed that inhibition of miR-340-5p facilitated osteogenic differentiation through regulating RUNX2 in MC3TC-E1 cells, which provided targeted therapeutic strategies for the treatment of DOP.
研究领域:
分子生物学
·
内分泌学
·
骨生物学
·
糖尿病研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2018
·Vol. 5
·期 4
·1700755
·
IF 12.441
Xuekun Fu,Yunyan Li,Tongling Huang,Zhiwu Yu,Kun Ma,Meng Yang,Qingli Liu,Haobo Pan,Huaiyu Wang,Junfeng Wang,Min Guan
Citrate is essential to biomineralization of the bone especially as an integral part of apatite nanocomposite. Citrate precipitate of apatite is hypothesized to be derived from mesenchymal stem/stromal cells (MSCs) upon differentiation into mature osteoblasts. Based on 13 C-labeled signals identified by solid-state multinuclear magnetic resonance analysis, boosted mitochondrial activity and carbon-source replenishment of tricarboxylic acid cycle intermediates coordinate to feed forward mitochondrial anabolism and deposition of citrate. Moreover, zinc (Zn 2+ ) is identified playing dual functions: (i) Zn 2+ influx is influenced by ZIP1 which is regulated by Runx2 and Osterix to form a zinc-Runx2/Osterix-ZIP1 regulation axis promoting osteogenic differentiation; (ii) Zn 2+ enhances citrate accumulation and deposition in bone apatite. Furthermore, age-related bone loss is associated with Zn 2+ and citrate homeostasis; whereas, restoration of Zn 2+ uptake alleviates age-associated declining osteogenic capacity and amount of citrate deposition. Together, these results indicate that citrate is not only a key metabolic intermediate meeting the emerging energy demand of differentiating MSCs but also participates in extracellular matrix mineralization, providing mechanistic insight into Zn 2+ homeostasis and bone formation.
研究领域:
生物学
·
生物化学
·
生物矿化
·
干细胞研究
·
骨科
✓ 已验证
DOI
PubMed
高影响因子
International Journal of Oral Science
·
2026
·Vol. 18
·期 1
·64
·
IF 17.6
Li Jie,Liu Yang,Qiao Yanchun,Yan Changqing,Zhao Weiwei,Ji Lingli,Liu Dandan,Xin Yuejiao,Zhang Chenying,Wang Xiaozhe,Wang Yixiang,Zheng Shuguo
Delayed tooth eruption is a hallmark of cleidocranial dysplasia (CCD) caused by RUNX2 haploinsufficiency, yet the underlying molecular mechanism remains undefined. Here, we show that RUNX2 regulates osteoclast-mediated alveolar bone remodeling, a process closely associated with tooth eruption. Runx2 +/− mice exhibit impaired osteoclast differentiation and reduced alveolar bone resorption, resulting in delayed mandibular molar eruption—a phenotype that recapitulates human CCD. Mechanistically, RUNX2 transcriptionally activates LncRNA-ROD ( Regulator of Osteoclast Differentiation ), which promotes osteoclastogenesis by sequestering QKI to stabilize Csf1r mRNA. LncRNA-ROD −/− mice phenocopy the eruption defects and reduced alveolar bone resorption observed in Runx2 +/− mice. Critically, both Runx2 +/− and LncRNA-ROD −/− mice show reduced osteoclast differentiation in alveolar bone, consistent with in vitro data from bone marrow-derived monocytes/macrophages demonstrating impaired osteoclast differentiation. Notably, rescue experiments in ovariectomy-induced osteoporosis models demonstrate that QKI knockdown restores osteoclast differentiation in Runx2 +/− and LncRNA-ROD −/− mice, highlighting the critical role of the RUNX2/ LncRNA-ROD /QKI axis in osteoclastogenesis. The axis supports alveolar bone remodeling associated with tooth eruption. These results provide mechanistic insights into cleidocranial dysplasia-related alveolar bone remodeling defects and delayed tooth eruption, and identify LncRNA-ROD as a potential therapeutic target for alveolar bone remodeling disorders. Furthermore, this axis is implicated in broader bone metabolic disorders, as demonstrated by its impact on osteoporosis progression in Runx2 +/− and LncRNA-ROD −/− mice.
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2021
·
IF 3.517
Caiyun Liu,Zhenzu Bai,Jiayu Lin,Kai Jiang,Shan Huang,Weijia Zheng,Ruifen Chen,Yang Xiang,Xiaoyan Wang,Long Liu
The application of 3 D printing technology in tissue engineering has become increasingly important. However, due to the limitations of bio-ink, there are still some remaining problems. For example, the major challenge for ideal bio-ink is to maintain stable 3 D structure and good biocompatibility in the meantime while conventional gels are week and nearly unprintable. So, the development of new bio-ink material with improved rheological and mechanical properties is highly demanded to avoid compromising biocompatibility for tissue engineering. Silk fibroin (SF), a natural degradable polymer, is considered to be a proper material for the preparation of bio-inks. We used SF, gelatin, and polyols as raw materials to fabricate bio-inks and scaffolds. We evaluated the rheological properties and printability of bio-inks with a rotational rheometer and a 3 D printer. The scaffolds were prepared by crosslinking and freeze-drying technologies. The biocompatibility and osteoinductive functions of scaffolds were investigated by evaluating proliferation, osteogenic differentiation and related cell signaling of cultured MC3T3-E1 cells. The results showed that the scaffolds using SF, Gel and propanediol (PG) not only had good rheological properties and storage modulus, but also could better enhance osteogenic specific genes expression mediated by Smad1/5/8 and Runx2 pathways. What is more, morphological characterization showed that α-mem incubation could help scaffold form porous structure on its surface, which could shed a light on a new 3 D bio-printed bone repair scaffold with both naturally emerged and CAD-designed porous structure. Our findings provide a potential biomaterial for the treatment of bone tissue regeneration.
研究领域:
生物医学工程
·
材料科学
·
组织工程
·
生物材料
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Cell and Developmental Biology
·
2020
·
IF 5.186
Zhai Qiaoli,Zhao Yi,Wang Linping,Dai Yan,Zhao Peiqing,Xiang Xinxin,Liu Kui,Du Wenyan,Tian Wenxiu,Yang Baoye,Li Tao,Wang Lianqing
Circular RNAs (circRNAs) are regarded as pivotal regulators in bone metabolism. However, the role of circRNAs in osteoblast mineralization remains largely unknown. Herein, we explored the expression profiles of circRNAs in 4 groups of osteoblasts with varying mineralization processes. Hsa_circ_0008500 (circ8500), which is upregulated in the RNA-seq data, is sifted through 194 candidate circRNAs in osteoblasts during mineralization. We characterize the features of novel circRNAs and find that the elevated expression of circ8500 promotes osteoblast mineralization. Mechanistically, circ8500 contains a critical binding site for miR-1301-3p. We further show that circ8500 competitively binds miR-1301-3p to abolish its suppressive effect on peptidyl arginine deiminase 4 (PADI4). PADI4 works as a binding partner of RUNX2 and stabilizes its protein expression levels by inhibiting the ubiquitin-proteasome pathway. This work provides new insights on the circRNA patterns in osteoblasts and the role of PADI4 in matrix mineralization.
研究领域:
分子生物学
·
骨代谢
·
基因组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR BIOCHEMISTRY
·
2019
·Vol. 121
·期 3
·2606-2617
·
IF 3.448
Yuzhuo Wang,Ying Li,Pu Shao,Liuyi Wang,Xingfu Bao,Min Hu
Cementum regeneration is considered the gold standard for the treatment of periodontitis. As one of the most important primary proinflammatory cytokines, interleukin 1β (IL1β) plays an essential role during the early stage of periodontitis and its amounts simultaneously increase dramatically during this stage. Though promising, the differentiation of cementoblasts upon IL1β-induced inflammation of the microenvironment and the relative interaction mechanism are still unknown. Here, we found that IL1β inhibited cementoblast differentiation and microRNA-325-3p (miR-325-3p) was increased during IL1β-stimulated cementoblasts. Bioinformatics analysis and luciferase reporter assay demonstrated miR-325-3p targeted runt-related transcription factor 2 directly. Transfection of miR-325-3p suppressed cementoblast differentiation in vitro and the formation of cementum-like tissues in vivo. The inhibitor of miR-325-3p could mitigate the above effects induced by IL1β. Accordingly, our finding suggests a critical role of miR-325-3p in linking inflammation to impaired cementum regeneration and provides a potential possibility for applying miR-325-3p inhibitors in the treatment of periodontitis-related bone loss.
研究领域:
口腔医学研究
·
分子生物学
·
炎症
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）