ACS Applied Materials & Interfaces
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2024
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IF 8.3
Wei Yang,Qin Zou,Chenxin Wang,Yuankun Ren,Rui Zhang,Mingyue Lin,Zeyu Huang,Mengxin Huangfu,Lili Lin,Wei Li,Xiyu Li
Bone scaffolds offer hope for oral jawbone repair, yet improving their osteogenic performance remains a clinical challenge. This study investigates a novel approach to enhance early bone formation and osteogenic quality by coloading hydroxyapatite (HA)─internalized osteoblasts (OHA) and osteonectin (ON) onto various scaffolds. Our findings demonstrated that the OHA could effectively facilitate the early bone regeneration by providing rapid calcium and phosphorus ion release via lysosome-mediated HA degradation, while the ON protein helps in ion deposition, cell proliferation, and matrix mineralization. When the PHA (PCL+HA) scaffold was incorporated with both the OHA and ON, the scaffold exhibited superior pro-osteogenic performance, driven by synergistic effects of rapid ion release from the OHA, slow ion release from the PHA, and upregulation of osteogenesis-related genes. The analyses of mechanisms revealed that the OHA activated MAPK and PI3K–Akt pathways, while ON stimulated calcium and Wnt signaling, collectively promoting the osteogenic potential. The strategy presented in this study paves a promising way for the development of advanced bone scaffolds to improve the bone regeneration quality.
研究领域:
生物医学工程
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组织工程
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骨科研究
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DOI
PubMed
高影响因子
Biomedical Engineering Online
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2024
·Vol. 23
·期 1
·1-10
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IF 2.9
Xie Cuncun,Jia Xiaodong,Ding Shaoguang,Ding Xiaoli,Wang Guangke,Liu Hongjian
Objectives To explore the expression of periostin in the epithelium of cholesteatoma with different destruction degrees of the ossicular chain and its clinical value in predicting postoperative hearing recovery. Methods Retrospective analysis was conducted on the clinical data of 100 patients with middle ear cholesteatoma (the cholesteatoma group) admitted to our hospital. Another 100 patients without middle ear cholesteatoma treated in our hospital during the same period were included in the non-cholesteatoma group. Middle ear cholesteatoma patients were further divided into a normal group, a partial destruction group, and a complete destruction group based on the destruction degree of the ossicular chain (Maresh grading). After the treatment, 75 cases were considered as the effective group and 25 cases as the ineffective group. The expression of tumor necrosis factor-alpha, Interleukin 6, and periostin in the epithelium of middle ear cholesteatoma patients with different destruction degrees of the ossicular chain and different therapeutic effects were compared. The correlation between periostin and inflammatory factors was analyzed using Pearson analysis. The predictive value of tumor necrosis factor-alpha, Interleukin 6, and periostin on treatment effect was valued using the receiver operating characteristic curve. Results Patients in the cholesteatoma group had a much higher content of tumor necrosis factor-alpha, Interleukin 6, and periostin than those in the non-cholesteatoma group ( P < 0.001). The expression of tumor necrosis factor-alpha, Interleukin 6, and periostin was also largely increased with the destruction group of the ossicular chain. Patients in the ineffective group had much higher expression of tumor necrosis factor-alpha, Interleukin 6, and periostin than those in the effective group ( P < 0.001). The Pearson correlation analysis results showed that periostin was positively correlated with the content of tumor necrosis factor-alpha and interleukin 6 ( P = 0.868, 0.880, P < 0.001). The areas under the curve of individual or joint tumor necrosis factor-alpha, Interleukin 6, and periostin were 0.627, 0.793, 0.822, and 0.892, respectively. Conclusions The expressions of periostin, Interleukin 6, and tumor necrosis factor-alpha were markedly increased in the epithelium of middle ear cholesteatoma patients, which were gradually increased with the aggravation of the ossicular chain destruction. Periostin, Interleukin 6, and tumor necrosis factor-alpha could be used as important indicators to predict postoperative hearing recovery.
研究领域:
耳科学
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分子生物学
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临床医学
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DOI
PubMed
高影响因子
FASEB JOURNAL
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2025
·Vol. 39
·期 9
·e70608
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IF 4.2
Wentao Liu,Yuan Wang,Chen Liu,Bowei Shi,Xiaowei Xiong,Sheng Chen,Qianqian Huang,Li Wang,Guohua Zeng,Qiren Huang
Atherosclerosis (AS) is the primary pathological basis of many cardiovascular diseases, and the formation of foam cells plays a critical role in the progression of AS. Increasing evidence shows that a considerable proportion of foam cells derive from vascular smooth muscle cells (VSMCs) in atherosclerotic plaques. Osteopontin (OPN), a glycosylated protein secreted by cells, is supposed to promote the development of AS. However, the underlying mechanisms of OPN contributing to the AS progression remain unclear. Therefore, the purpose of the study is to investigate the effects and mechanisms of OPN on VSMC-foaming and AS. Mouse AS model was established by feeding ApoE −/− mice with high fat diet (HFD), and the foam cell model of murine aortic vascular smooth muscle cells (MOVAS) was induced with Ox-LDL. During modeling, both ApoE −/− mice and MOVAS were infected with mouse recombinant adenoviruses expressing OPN (Ad-OPN). Our results show that OPN aggravates vascular smooth muscle dysfunction and AS in the ApoE −/− mice fed with HFD. Besides, OPN reduces cholesterol efflux and further promotes the formation of VSMC-derived foam cells by decreasing the expressions of ABCA1 and ABCG1. Furthermore, OPN inhibits the phosphorylation of p38MAPK through binding to its membrane receptor CD44, thereby reducing the expressions of LXRα, ABCA1, and ABCG1. Our results demonstrate that OPN reduces the expression of cholesterol transporters ABCA1 and ABCG1 and promotes the formation of VSMC-derived foam cells, exacerbating the development of AS. The findings would provide a more powerful theoretical support for preventing and treating AS with OPN as the target. Graphical OPN binding to CD44 inhibits the phosphorylation of p38MAPK, thereby reducing the expression of downstream LXRα, ABCA1, and ABCG1, resulting in decreased cholesterol efflux and increased foaming of VSMCs, ultimately exacerbating atherosclerosis.
研究领域:
心血管疾病
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分子生物学
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DOI
PubMed
高影响因子
Analytical Methods
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2025
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IF 2.6
Xue Kong,Yan Liu,Jinghui Lyu,Zheng-Zhi Yin,Yi Zhang
Osteopontin (OPN) is an important biomarker for reflecting osteoarthritic inflammation and endochondral ossification. In the field of electroanalysis, OPN belongs to non-electroactive protein, which is usually detected by means of an outer probe or biolabel. Here, a novel microsensor can directly electroanalyze OPN, which was constructed by coordinating surface molecularly imprinted polymer (SMIP) with a built-in electroactive probe of poly (methylene blue) (pMB) on an acupuncture needle microelectrode (ANME). The OPN template can be reversibly anchored using 4-mercaptophenylboric acid (4-MBPA) via a borate bond between phenylboronic acid and the external cis-diol of the glycoprotein. Methylene blue (MB) and dopamine (DA) were sequentially electropolymerized and grown around templates, which played pivotal roles in the detection signal from the built-in pMB through the imprinted nanocavities. After the recombination of OPN molecules with imprinted nanocavities, the current strength of built-in pMB could be impeded with a highly sensitive response. This microsensor shows a linear relationship to the concentration of OPN from 0.01 to 1000 ng mL-1 with a detection limit of 3 pg mL-1. The microsensor also exhibits high selectivity and stability, which is attributed to the recognizing ability of the imprinted nanocavities and the hindrance and anti-interference function of coated polydopamine (pDA). This strategy of preparing a sensor shows practical and scientific significance for functionalizing microelectrodes and constructing microsensors for non-electroactive glycoproteins. In the future, it will be fascinating to integrate this microsensor with the acupuncture technique.
研究领域:
生物医学工程
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分析化学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Xinyuan Liu,Xin Liu,Wanqiu Xue,Quan-Li Li,Leping Wu,Chris Ying Cao
Collagen fibers reinforced by hydroxyapatite (HA) constitute the fundamental structures of natural bone and dentin, where non-collagenous proteins (NCPs) play a regulatory role in collagen fiber mineralization. However, the precise mechanism underlying this mineralization process remains controversial. Moreover, achieving mineralized materials with high-purity, high-mimetic, and high-efficiency, as well as elucidating the essential state of mineralized precursor, are key issues in making a breakthrough in collagen fiber mineralization. Herein, an osteopontin phosphorylated polypeptide (OPP) was designed to explore the biomimetic mineralization of collagen fibers through mineralized ion stabilization and collagen surface modification. OPP could stabilize calcium and phosphate, forming OPP-prenucleation clusters (OPP-PNCs) with small sizes and long-term stabilization. Additionally, OPP could bind to and modify collagen fibers, thereby reducing the interfacial energy. Compared to Bare-Collagen, OPP-Collagen remarkably enhanced the mineralization efficiency. Molecular dynamics simulations indicated that OPP-Collagen could sequester calcium and phosphate from OPP-PNCs to induce mineralization, while Bare-Collagen lacks this ability. This biomimetic mineralization strategy utilizing OPP-PNCs achieved both intrafibrillar and extrafibrillar mineralization of OPP-collagen fibers. The present study introduces a novel OPP-Collagen mineralization strategy that highlights the regulatory role of NCPs on the surface of natural collagen, offering valuable perspectives into the mechanisms underlying natural mineralization processes.
研究领域:
生物材料学
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分子生物学
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骨组织工程
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
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2024
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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
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分子生物学
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药理学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF HISTOCHEMISTRY
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2023
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IF 2
Jing Guo,Chang-Yong Tong,Jian-Guang Shi,Xin-Jian Li,Xue-Qin Chen
Lung cancer is prone to bone metastasis, and osteopontin (OPN) has an important significance in maintaining bone homeostasis. The goal of this study was to explore the impact of OPN level on bone metabolism and the molecular mechanism of inhibiting bone metastasis in non-small cell lung cancer (NSCLC). The expression of OPN in NSCLC was ascertained by Western blot and immunohistochemistry, and the correlation between the expression level of OPN and survival of patients was analyzed. Then the shRNA technology was applied to reduce the expression of OPN in NSCLC cells, and CCK-8 assay was carried out to investigate the effect of low expression of OPN on the proliferation of NSCLC cells. In addition, the effects of low expression of OPN on osteoclast differentiation, osteoblast generation and mineralization were studied using osteoclast precursor RAW264.7 and human osteoblast SaOS-2 cells, and whether OPN could regulate miR-34c/ Notch pathway to affect bone metabolism was further explored. The findings showed that the high level of OPN in NSCLC was closely related to the poor prognosis of patients and the abnormal proliferation of NSCLC cell lines. The suppression of OPN was beneficial to inhibit the differentiation of osteoclasts and promote the mineralization of osteoblasts. Besides, this study confirmed that the deletion of OPN can regulate bone metabolism through the regulation of miR-34c/Notch1 pathway, which will contribute to inhibiting the occurrence of osteolytic bone metastasis in NSCLC.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2025
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IF 13.2
Guanlu Shen,Xinxin Si,Lei Qiang,Yihao Liu,Zhiyang Yin,Jing Shan,Pengfei Zheng
Growth plate injuries in children and adolescents often lead to bone bridge formation, resulting in limb deformities due to the limited self-repair capacity of the growth plate. The limitations of traditional treatments prompted interest in the role of the extracellular matrix (ECM) and mechanical environment in tissue repair. Recent research showed that 3D hydrogels could mimic ECM to regulate mesenchymal stem cells (MSCs) differentiation, with MSCs sensing matrix viscoelasticity via Piezo1 and responding through the ROCK signaling pathway. This study aimed to develop a 3D biomimetic hydrogel composed of acellular cartilage matrix methacryloyl (ACMMA) and gelatin methacryloyl (GelMA), with adjustable viscoelasticity via blue light crosslinking time. Hydrogels with low (5 s) and high (20s) modulus were fabricated and loaded with bone marrow mesenchymal stem cells (BMSCs). Results demonstrated that the 5 s hydrogel promoted chondrogenic differentiation and inhibited osteogenesis, effectively preventing bone bridge formation and enhancing growth plate repair in vivo . Mechanistic studies confirmed that the 5 s group did not activate the Piezo1-ROCK pathway, supporting its role in chondrogenic differentiation.
研究领域:
生物医学工程
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组织工程
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干细胞研究
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生物材料
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骨科
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DOI
高影响因子
ANALYTICA CHIMICA ACTA
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2024
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IF 5.7
Qin Weng,Hang Li,Zhichao Fan,Yan Dong,Yuchen Qi,Peilin Wang,Cheng Luo,Jianjun Li,Xiang Zhao,Hua Yu
Background Osteopontin (OPN) is closely associated with tumorigenesis, growth, invasion, and immune escape and it serves as a plasma biomarker for hepatocellular carcinoma (HCC). Nevertheless, the accurate and rapid detection of low-abundance OPN still poses significant challenges. Currently, the majority of protein detection methods rely heavily on large precision instruments or involve complex procedures. Therefore, developing a simple, enzyme-free, rapid colorimetric analysis method with high sensitivity is imperative. Results In this study, we have developed a portable colorimetric biosensor by integrating the triple-helix aptamer probe (THAP) and catalytic hairpin assembly (CHA) strategy, named as T-CHA. After binding to the OPN, the trigger probe can be released from THAP, then initiates the CHA reaction and outputs the signal through the formation of a G-quadruplex/Hemin DNAzyme with horseradish peroxidase-like activity. Consequently, this colorimetric sensor achieves visual free-labeled detection without additional fluorophore modification and allows for accurate quantification by measuring the optical density of the solution at 650 nm. Under optimal conditions, the logarithmic values of various OPN concentrations exhibit satisfactory linearity in the range of 5 pg mL −1 to 5 ng mL −1 , with a detection limit of 2.04 pg mL −1 . Compared with the widely used ELISA strategy, the proposed T-CHA strategy is rapid (∼105 min), highly sensitive, and cost-effective. Significance The T-CHA strategy, leveraging the low background leakage of THAP and the high catalytic efficiency of CHA, has been successfully applied to the detection of OPN in plasma, demonstrating significant promise for the early diagnosis of HCC in point-of-care testing. Given the programmability of DNA and the universality of T-CHA, it can be readily modified for analyzing other useful tumor biomarkers.
研究领域:
生物标志物检测
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癌症诊断
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分子生物学
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生物技术
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2025
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IF 4.9
Qingfeng Luo,Yuyi Deng,Qiyuan Yang,Nanxin Zhao,Can Wang,Xingsheng Li
Osteopontin (OPN), highly expressed in foam cells, serves as a hallmark of atherosclerotic plaques and a potential target for site-specific drug delivery. In this study, we developed OPN-targeted liposomes (OPN LIP) co-loaded with curcumin and perfluoro-n-pentane (PFP) to enhance therapeutic efficacy against atherosclerosis. The liposomes exhibited uniform particle size, colloidal stability, favorable biocompatibility, and minimal cytotoxicity. In vitro experiments demonstrated efficient and time-dependent cellular uptake by ox-LDL–stimulated RAW264.7 foam cells. Upon exposure to low-intensity focused ultrasound (LIFU), the nanocarriers underwent acoustic cavitation-induced rupture, leading to rapid curcumin release and significant induction of apoptosis. OPN LIP treatment notably reduced IL-1α and TNF-α levels and aggravated apoptosis in foam cells. Transcriptomic analysis revealed modulation of inflammatory and apoptotic pathways, including TLR, NF-κB, and Mapk3 signaling. These findings highlight the potential of OPN LIP as an ultrasound-responsive, targeted nanoplatform capable of suppressing inflammation and foam cell viability, providing a promising approach for the treatment of atherosclerosis through combined physical and pharmacological strategies.
研究领域:
纳米医学
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心血管疾病
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药物递送
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超声治疗
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炎症生物学
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细胞凋亡研究
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Junxian Hu,Yibo Zhu,Xiaoxiao Li,Zeyu Pang,Xiangwei Li,Huilin Zhang,Yiyang Wang,Pei Li,Qiang Zhou
Medical and conservative treatments for intervertebral disc degeneration (IDD) primarily focus on alleviating symptoms. However, effective curative therapies that promote disc regeneration remain lacking. Recent advancements in disc repair materials offer a potential solution, but identifying effective cytokines for regeneration and developing efficient drug delivery systems are crucial for success. This study demonstrated a negative correlation between AQP3 expression levels and the extent of disc degeneration induced by mechanical overload, as evidenced in both in vivo and in vitro models, suggesting that AQP3 is a key regulator of intervertebral disc (IVD) homeostasis. Moreover, the overexpression of AQP3 or exogenous AQP3 protein significantly repaired degenerated IVDs. As a membrane protein, exogenous AQP3 is challenging for cells to recognize and internalize. To address this issue, we designed liposomes to encapsulate AQP3 and incorporated them into GelMA (AQP3-lipo@GelMA) for targeted repair of IDD resulting from high mechanical pressure. The encapsulation of AQP3 in liposomes improved cellular recognition and uptake, thereby enhancing its functionality at the cell membrane. Additionally, AQP3 within this material inhibited the binding of integrins to sialic acid-binding proteins (IBSP), which subsequently reduced the expression of the downstream integrin αVβ3. This cascade effect indirectly activated the AKT pathway, promoting the survival of NP cells. In vivo experiments, we found that AQP3-lipo@GelMA had an efficient function of repairing degenerated intervertebral disc. This study introduced AQP3-lipo@GelMA as a promising material for clinical applications in IVD repair.
研究领域:
再生医学
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骨科
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生物材料科学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
FOOD HYDROCOLLOIDS
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2023
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IF 10.7
Yuqin Huang,Zerong Lu,Feitong Liu,Jonathan Lane,Juchun Chen,Xiong Fu,Qiang Huang,Ruibiao Hu,Bin Zhang
Encapsulation is usually adapted to improve probiotic viability under adverse environmental conditions, and used to ensure adequate amount of probiotics reach the distal gastrointestinal tract and achieve probiotic action. In the present study, sub-species of Bifidobacterium were encapsulated with pectin or alginate by an emulsification/internal gelation method. Bovine milk osteopontin (OPN) was used as an excipient with potential to improve the protection of the probiotics during processing and/or gastrointestinal digestion. Here, we reported that the use of OPN significantly improved probiotic viability during freeze drying and simulated infant gastrointestinal digestion. The viability of Bifidobacterium bifidum R0071 and Bifidobacterium breve M-16V loaded in pectin-based freeze-dried microcapsules with 0.5% OPN addition remained at over 10 6 CFU·g −1 after simulated infant digestion. In comparison, the microcapsules without OPN had a probiotic viability of only 10 3 CFU·g −1 . The protective effect of OPN was proven to be dose dependent. For example, the B. bifidum R0071 viability was 6.1 log CFU·g −1 after the gastrointestinal digestion for the pectin-based microencapsulation without OPN addition, while the value remained at 8.4 log CFU·g −1 when OPN concentration reached 5%. In this study, we also demonstrated that extracellular calcium ions could chelate with OPN molecules which could be attributed to preventing damage of the probiotic cell wall and the improved protective effective of microencapsulation. Overall, these results provide new insight into the use of OPN as a microencapsulation excipient to promote probiotic viability and its potential future application in functional foods such as infant formula with enhanced gut health.
研究领域:
食品科学
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营养学
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微生物学
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生物技术
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）