Doklady Biochemistry and Biophysics
·
2021
·Vol. 497
·期 1
·123-129
·
IF 0.788
Zhao Liang,Luo Yuming,Wang Yijun,Zhao Fujian,Chen Xiaofeng,Cai Daozhang
Abstract This study aimed to evaluate if the 3D printed bioactive glass porous scaffolds (BGS) can improve the reconstruction of the large bone defect. A rabbit model of large bone defects was established by making a 1.0 or 1.5 cm segmental defect in the middle of the femur bone. Then a 1.0 or 1.5 cm BGS was implanted into the bone defect. X-ray imaging showed that in both 1.0 and 1.5 cm groups, the newly formed bone tissue could be observed at 4 weeks after implantation, but a strengthened ossification trend could be observed at different time points. In the 1.0 cm group, a larger number of newly formed bone tissues were observed at 4 weeks, and in the 1.5 group, more newly formed bone tissues were found at 8 weeks. Nevertheless, ossified tissue generation on the BGS mainly completed at 12 weeks after implantation in both groups. The H&E staining revealed that the 3D BGS was easily degraded to form osteoid-like material in vivo , where the neo-ossification gradually occurred from the edge to the center. Immunohistochemical analysis showed that in the 1.0 group, protein expressions of three osteogenesis-related genes- BMP, collagen I and RUNX-2-all peaked at 8 weeks, and then gradually decreased at 12 and 18 weeks. In the 1.5 group, BMP and collagen I peaked at 18 weeks.
研究领域:
骨科
·
组织工程
·
材料科学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Bioscience-Landmark
·
2024
·Vol. 29
·期 11
·389
·
IF 3.3
Jie Dai,Haiyan Huang,Liucheng Wu,Mei Ding,Xiangyang Zhu
Background: Vitamin D receptor (VDR) can prevent myocardial ischemia reperfusion injury (MIRI). Hence, we aimed to illuminate the effect of VDR on cerebral ischemia/reperfusion injury (CIRI). Methods: C57BL/6 mice and SK-N-SH cells were utilized to establish CIRI and cellular oxygen deprivation/reoxygenation (OGD/R) models. Mice were injected with 1 μg/kg Calcitriol or 1 μg/kg Paricalcitol (PC) and adenovirus-mediated VDR overexpression or knockdown plasmids. 2,3,5-triphenyl-tetrazolium chloride (TTC) and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays were performed to measure the brain infarct volume and the apoptosis of cerebral cells. SK-N-SH cells were treated with 5 mM N-acetyl-L-cysteine (NAC) and transfected with VDR knockdown plasmid. Flow cytometry and Cell Counting Kit-8 (CCK-8) assays were employed to assess the apoptosis and cell viability. Enzyme-Linked Immunosorbent Assay (ELISA), quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) and Western blot were exploited to quantify the levels of reactive species oxygen (ROS), other oxidative stress-related factors, VDR and apoptosis-related factors. Results: The level of VDR in mouse cerebral tissue was elevated by CIRI (p < 0.001). CIRI-induced cerebral infarction (p < 0.001) and the apoptosis of cerebral cells (p < 0.001) in mice were mitigated by the activation of VDR. VDR overexpression abrogated while VDR silencing enhanced CIRI-induced infarction, oxidative stress and apoptosis of cerebral cells (p < 0.05). Furthermore, VDR silencing aggravated the oxidative stress and apoptosis in OGD/R-treated SK-N-SH cells (p < 0.05). NAC, a scavenger of oxidative stress, could reverse the effects of VDR silencing on apoptosis and oxidative stress in OGD/R-treated SK-N-SH cells (p < 0.01). Conclusion: VDR alleviates the oxidative stress to protect against CIRI.
研究领域:
神经科学
·
药理学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2025
·
IF 5.2
Dazhen Zhang,Xinzhe Qu,Fuchao Chu,Zhenxin Wang,Jie Mou,Feng Yuan
Background Heterotopic ossification (HO) is characterized by abnormal bone formation outside the skeleton following injury or inherited disease, leading to limb dysfunction and neurological deficits. Current treatment options for HO are largely ineffective. Methods A network pharmacological analysis was conducted to identify the active ingredients and protein targets in Astragalus and Cinnamon Twig Five-Substance Decoction (ACTFSD) on HO. Protein-protein interaction analysis and Gene Ontology Enrichment Analysis were used to investigate the key genes associated with the target proteins. Molecular docking was employed to validate the interactions between the core components and targets of ACTFSD. Kaempferol was encapsulated in liposomes synthesized via the thin-film dispersion method. In vitro and in vivo experiments were conducted to evaluate the therapeutic effects of kaempferol liposomes. Results Kaempferol, an active ingredient in ACTFSD, effectively inhibits the PTGS2\ NF-κB pathway, regulates macrophage immune responses, and reduces cytokine released by macrophages induce abnormal osteogenesis in tendon stem cells (TDSCs), thereby slowing the formation of HO. Kaempferol liposomes demonstrate better therapeutic effect than kaempferol alone. Conclusion This study indicates that targeting macrophages may represent an effective therapeutic strategy for HO. Furthermore, kaempferol liposomes appear to be a promising treatment for trauma-induced HO. These findings provide potential new directions for future HO treatment strategies.
研究领域:
医学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2020
·
IF 8.724
Jie Shen,Bo Chen,Xinyun Zhai,Wei Qiao,Shuilin Wu,Xuanyong Liu,Ying Zhao,Changshun Ruan,Haobo Pan,Paul K. Chu,Kenneth M.C. Cheung,Kelvin W.K. Yeung
The fate of cells and subsequent bone regeneration is highly correlated with temporospatial coordination of chemical, biological, or physical cues within a local tissue microenvironment. Deeper understanding of how mammalian cells react to local tissue microenvironment is paramount important when designing next generation of biomaterials for tissue engineering. This study aims to investigate that the regulation of magnesium cationic (Mg 2+ ) tissue microenvironment is able to convince early-stage bone regeneration and its mechanism undergoes intramembranous ossification. It was discovered that moderate Mg 2+ content niche (~4.11 mM) led to superior bone regeneration, while Mg 2+ -free and strong Mg 2+ content (~16.44 mM) discouraged cell adhesion, proliferation and osteogenic differentiation, thereby bone formation was rarely found. When magnesium ions diffused into free Mg zone from concentrated zone in late time point, new bone formation on free Mg zone became significant through intramembranous ossification. This study successfully demonstrates that magnesium cationic microenvironment serves as an effective biochemical cue and is able to modulate the process of bony tissue regeneration. The knowledge of how a Mg 2+ cationic microenvironment intertwines with cells and subsequent bone formation gained from this study may provide a new insight to develop the next generation of tissue-repairing biomaterials.
研究领域:
组织工程
·
生物材料
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELLULAR AND MOLECULAR LIFE SCIENCES
·
2024
·Vol. 81
·期 1
·1-16
·
IF 6.2
Zhao Yongzhao,Chen Longting,Xiang Qian,Lin Jialiang,Jiang Shuai,Li Weishi
Background The ligamentum flavum (LF) is an important anatomical structure of the spine. Ossification of the LF (OLF) has become the leading cause of thoracic spinal stenosis. Circular RNAs (circRNAs) and N6-methyladenosine (m6A) modification are reported to be associated with several human diseases. However, the role of circRNAs and m6A modification in the pathogenesis of OLF has not been fully investigated. Here, we aimed to explore the vital function of circRNAs and m6A modification in OLF. Materials and methods We analysed the circRNA expression of 4 OLF tissues and 4 normal LF tissues using bioinformatic analysis and identified circCDK14 for further analysis. We investigated the effects of circCDK14 on the osteogenic differentiation of LF cells. We observed that circCDK14 regulated its target genes by binding to miRNAs as a miRNA sponge. Moreover, the circRNA pull-down assay indicated that RNA-binding proteins might regulate the expression of circCDK14 via m6A modification. Results CircCDK14 was significantly upregulated in OLF tissues compared to normal LF tissues. Overexpression of circCDK14 promoted the osteogenic differentiation of LF cells. Mechanistically, CircCDK14 promoted the expression of ALF transcription elongation Factor 4 (AFF4) by serving as a sponge for miR-93-5p. Moreover, Wilms tumour 1-associated protein (WTAP) increased the stability of circCDK14 via N6-methyladenosine modification. Conclusion The m6A-modified CircCDK14 binding to miR-93-5p played an important role in the osteogenesis of LF cells by targeting AFF4, providing a promising therapeutic target for OLF.
研究领域:
分子生物学
·
表观遗传学
·
骨科
·
生物信息学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2017
·
IF 3.887
Min He,Qian Wang,Zhenqiang Shi,Yi Xie,Weifeng Zhao,Changsheng Zhao
Heterotopic ossification(HO) is a potential severe complication after many biomaterial implanting surgeries, and the inflammation environment caused by the implanting-associated infections is considered as the main nosogenesis. Herein, an inflammation-responsive drug release system was designed by chemically conjugating indometacin (via ester group) onto hydrogel coating to realize local self-regulated drug release to prevent HO. In our strategy, poly(3-mercaptopropyl)trimethoxysilane-co-acrylic acrylate and polyvinyl alcohol (providing anchoring sites for drug molecules) were firstly synthesized and functionalized with ene-groups, then a hydrogel layer was formed and covalently attached onto thiol-modified substrate via thiol-ene click chemistry, followed by grafting indometacin. A porous structure of the attached hydrogel layer was observed by scanning electron microscopy, and the presence of drug molecules in the hydrogel layer was confirmed by X-ray photoelectron spectroscopy and UV–vis absorption spectra . The drug release could be triggered under the mimicking inflammation environment, and the release rate was responsive to the inflammation degree. In addition, after attaching the hydrogel coating, the substrate showed low cytotoxicity, and high promotion for cell adhesion and proliferation. The excellent hemocompatibility of the hydrogel coating was also demonstrated by prolonged clotting time and suppressed platelet adhesion. This work suggests that the inflammation-responsive indometacin conjugated hydrogel coating has great potential to be used for prophylaxis HO.
研究领域:
生物材料学
·
药剂学
·
组织工程学
✓ 已验证
DOI
PubMed
高影响因子
Antioxidants
·
2022
·Vol. 11
·期 6
·1044
·
IF 7.675
Yuanying Li,Pengpeng Zhang,Zhoutong Sun,Huanhuan Li,Ran Ge,Xiang Sheng,Wuyuan Zhang
Calcitriol is an active analog of vitamin D3 and has excellent physiological activities in regulating healthy immune function. To synthesize the calcitriol compound, the concept of total synthesis is often adopted, which typically involves multiple steps and results in an overall low yield. Herein, we envisioned an enzymatic approach for the synthesis of calcitriol. Peroxygenase fromAgrocybe aegerita(AaeUPO) was used as a catalyst to hydroxylate the C-H bond at the C-25 position of alfacalcidol and yielded the calcitriol in a single step. The enzymatic reaction yielded 80.3% product formation in excellent selectivity, with a turnover number up to 4000. In a semi-preparative scale synthesis, 72% isolated yield was obtained. It was also found thatAaeUPO is capable of hydroxylating the C-H bond at the C-1 position of vitamin D3, thereby enabling the calcitriol synthesis directly from vitamin D3.Keywords:peroxygenases;oxyfunctionalization;active vitamin D;calcitriol;biocatalysis
研究领域:
生物化学
·
药物合成
·
酶工程
✓ 已验证
DOI
PubMed
高影响因子
Nature Communications
·
2021
·Vol. 12
·期 1
·1-12
·
IF 14.919
Jin Wenjing,Lin Xianfeng,Pan Haihua,Zhao Chenchen,Qiu Pengcheng,Zhao Ruibo,Hu Zihe,Zhou Yanyan,Wu Haiyan,Chen Xiao,Ouyang Hongwei,Xie Zhijian,Tang Ruikang
Osteoclasts (OCs), the only cells capable of remodeling bone, can demineralize calcium minerals biologically. Naive OCs have limitations for the removal of ectopic calcification, such as in heterotopic ossification (HO), due to their restricted activity, migration and poor adhesion to sites of ectopic calcification. HO is the formation of pathological mature bone within extraskeletal soft tissues, and there are currently no reliable methods for removing these unexpected calcified plaques. In the present study, we develop a chemical approach to modify OCs with tetracycline (TC) to produce engineered OCs (TC-OCs) with an enhanced capacity for targeting and adhering to ectopic calcified tissue due to a broad affinity for calcium minerals. Unlike naive OCs, TC-OCs are able to effectively remove HO both in vitro and in vivo. This achievement indicates that HO can be reversed using modified OCs and holds promise for engineering cells as “living treatment agents” for cell therapy.
研究领域:
骨科
·
细胞生物学
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Bo Xu,Suohui Zhang,Han Liu,Guozhong Yang,Zequan Zhou,Yunhua Gao
Osteoporosis is one of the most common diseases affecting the elderly, particularly postmenopausal women. It significantly increases the risk of fractures, reduces quality of life, and adds to the medical burden. Traditional formulations, such as alfacalcidol (ALF) capsules and tablets, have limitations, including difficulties in swallowing and patient resistance to long-term medication use, highlighting the urgent need for a sustained-release ALF formulation. To address this, we developed a double-layered core-shell microneedle patch integrated with ALF-loaded microparticles for the long-acting treatment of osteoporosis. This system aims to reduce administration frequency and improve patient compliance. After application for just 5 min, the patch can be removed, leaving the microneedle tips embedded in the skin. The core-shell structure of the tip consists of a core made of ALF-loaded polylactic- co -glycolic acid (PLGA) microparticles and a shell composed of ethylcellulose (EC). This structure acts as a drug reservoir within the skin, enabling for sustained release of ALF over 14 days. Compared to commercially available ALF tablets which require daily administration, the long-acting ALF double-layered core-shell microneedle patch (ALF-DCSMN) delivers a lower systemic drug dose while demonstrating comparable or better efficacy in increasing bone mass and improving trabecular microstructure. Notably, ALF-DCSMN only requires semimonthly administration. Overall, these promising results suggest that the ALF-DCSMN is a safe, effective, and user-friendly transdermal formulation for the long-acting treatment of osteoporosis.
研究领域:
药剂学
·
生物医学工程
·
骨科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Aging-US
·
2021
·
IF 5.682
Anlong Jiang,Nanxiang Wang,Xinxing Yan,Yunheng Jiang,Chengchao Song,Hui Chi,Guanghua Chen,Feng Wu,Ye Ji,Jinglong Yan
Ossification of the posterior longitudinal ligament (OPLL) is a disorder with multiple pathogenic mechanisms and leads to different degrees of neurological symptoms. Recent studies have revealed that non-coding RNA (ncRNA), including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), could influence the development of OPLL. Nevertheless, the molecular mechanisms linking circular RNAs (circRNAs) and the progression of OPLL is still unknown. The current research explored the expression profiles of OPLL-related circRNAs by microarray analysis, and applied qRT-PCR to validate the results. Subsequently, we confirmed the upregulation of hsa_circ_0007292 in OPLL cells by qRT-PCR and validated the circular characteristic of hsa_circ_0007292 by Sanger sequencing. Fluorescence in situ hybridization (FISH) unveiled that hsa_circ_0007292 was predominantly located in the cytoplasm. Functionally, gain-of-function and loss-of-function experiments showed that hsa_circ_0007292 promoted the osteogenic differentiation of OPLL cells. Mechanistically, the interaction of hsa_circ_0007292 and miR-508-3p was predicted and validated by bioinformatics analysis, dual-luciferase reporter assays, and Ago2 RNA immunoprecipitation (RIP). Similarly, we validated the correlation between miR-508-3p and SATB2. Furthermore, rescue experiments were performed to prove that hsa_circ_0007292 acted as a sponge for miR-508-3p, and SATB2 was revealed to be the target gene of miR-508-3p. In conclusion, our research shows that hsa_circ_0007292 regulates OPLL progression by the miR-508-3p/SATB2 pathway. Our results indicate that hsa_circ_0007292 can be used as a promising therapeutic target for patients with OPLL.
研究领域:
分子生物学
·
遗传学
·
骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS APPLICATIONS
·
2022
·
IF 2.712
Jialiang Lin,Junchao Huang,Jiang Wu,Bo Tang,Congbin Li,Haijun Xiao
Traumatic heterotopic ossification (THO) is a serious and common clinical post-traumatic complication for which there is no effective and safe drug treatment. Routine administration of nonsteroidal anti-inflammatory drugs (NSAIDs) after injury is extensively used approach for THO. However, serious adverse events can occur in the event of an overdose of NSAIDs. In our study, we have developed a poly(lactic acid-co-glycolic acid) (PLGA) microsphere by emulsifying solvent volatilization for the prolonged slow delivery of celecoxib (CLX). Three groups of celecoxib-poly(lactic acid-co-glycolic acid) microspheres (CLX–PLGA MPs) were prepared with particle sizes of 3.75±1.28 μm, 49.56±17.15 μm, and 94.98±42.53 μm. Meanwhile, related parameters of microspheres in each group were studied: drug loading (DL), encapsulation rate (EE), and slow-release behavior. The DL and EE of the 3 CLX–PLGA MPs did not vary significantly, and subsequently, we selected the second drug loading microspheres with a retardation period of about 70 days for subsequent experiments. Moreover, cellular and animal experiments suggest that the microspheres are biocompatible and can be safely applied to localized trauma tissue. Finally, it is demonstrated that CLX–PLGA MPs have an effect on inhibiting the osteogenic differentiation of bone marrow mesenchymal stem cells and have the potential to inhibit ectopic bone formation of the THO model in Sprague-Dawley rat. Therefore, this study suggests that CLX–PLGA MPs are expected to be applied topically in the early post-traumatic period to prevent the development of THO.
研究领域:
药理学
·
生物医学工程
·
骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2023
·
IF 15.1
Dan Li,Yucan Jiang,Ping He,Yeming Li,Yan Wu,Wei Lei,Nanxin Liu,Joost D. de Bruijn,Hua Zhang,Hongmei Zhang,Ping Ji,Huipin Yuan,Mingzheng Li
Heterotopic ossification (HO) is a double-edged sword. Pathological HO presents as an undesired clinical complication, whereas controlled heterotopic bone formation by synthetic osteoinductive materials shows promising therapeutic potentials for bone regeneration. However, the mechanism of material-induced heterotopic bone formation remains largely unknown. Early acquired HO being usually accompanied by severe tissue hypoxia prompts the hypothesis that hypoxia caused by the implantation coordinates serial cellular events and ultimately induces heterotopic bone formation in osteoinductive materials. The data presented herein shows a link between hypoxia, macrophage polarization to M2, osteoclastogenesis, and material-induced bone formation. Hypoxia inducible factor-1 α (HIF-1 α ), a crucial mediator of cellular responses to hypoxia, is highly expressed in an osteoinductive calcium phosphate ceramic (CaP) during the early phase of implantation, while pharmacological inhibition of HIF-1 α significantly inhibits M2 macrophage, subsequent osteoclast, and material-induced bone formation. Similarly, in vitro, hypoxia enhances M2 macrophage and osteoclast formation. Osteoclast-conditioned medium enhances osteogenic differentiation of mesenchymal stem cells, such enhancement disappears with the presence of HIF-1 α inhibitor. Furthermore, metabolomics analysis reveals that hypoxia enhances osteoclastogenesis via the axis of M2/lipid-loaded macrophages. The current findings shed new light on the mechanism of HO and favor the design of more potent osteoinductive materials for bone regeneration.
研究领域:
生物材料
·
骨生物学
·
组织工程
·
细胞生物学
✓ 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）