MATERIALS & DESIGN
·
2024
·
IF 7.6
Honglin Xiang,Chuan Zhang,Yongfu Xiong,Yong Wang,Chaoyu Pu,Jiangtao He,Lu Chen,Ke Jiang,Weikang Zhao,Hanfeng Yang,Fan Wang,Yuling Li
Osteoarthritis (OA) is characterized by cartilage degradation, inflammatory responses, and osteophyte formation. Matrix metalloproteinase 13 (MMP13) is a hallmark of OA development, and increased MMP13 expression is closely associated with extracellular matrix degradation. MMP13 expression varies significantly at different stages of OA progression. While cyclooxygenase 2 (COX-2) inhibitors are commonly used to treat OA, their long-term systemic administration increases the risks of adverse effects. Therefore, with the aim of achieving localized and responsive delivery of the COX-2 inhibitor celecoxib, the current study investigated an innovative MMP13-responsive micro-nano hydrogel microsphere system. Celecoxib-loaded cationic liposomes are non-covalently attached within the microsphere, enabling controlled drug release for OA treatment. In an OA environment with elevated MMP13 expression, the system is degraded via the action of MMP13 substrate peptide (MMP13sp), facilitating accelerated release of drug-loaded liposomes to improve the inflammatory microenvironment and treat OA rapidly. Compared to a phosphate-buffered saline solution with hyaluronidase (HAase), the prepared hyaluronic acid methacrylate microspheres HAMA/MMP13sp/Lipo@celecoxib exhibited rapid degradation in a solution containing a physiological concentration of MMP13/HAase, demonstrating specific enzyme responsiveness for precise anti-inflammatory drug release. The MMP13-responsive hydrogel microsphere system achieves intelligent and controllable drug release in OA, effectively decelerating disease progression and promoting articular cartilage repair.
研究领域:
药理学
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生物医学工程
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骨科
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2023
·Vol. 33
·期 16
·2213019
·
IF 19
Zhao Tianyuan,Deng Haoyuan,Li Jianwei,He Songlin,Li Xu,Li Hao,Yang Zhen,Deng Haotian,Li Peiqi,Sui Xiang,Jiang Shuangpeng,Guo Quanyi,Liu Shuyun
Despite numerous attempts to engineer cartilage tissue in recent years, significant challenges remain regarding hyaline cartilage regeneration. One main reason is that the overactivated inflammatory response after injury suppresses inherent cartilage regenerative capabilities. Since the arthritic microenvironment is constantly changing during posttraumatic stress, an inflammatory diagnostic logic-based hydrogel for cartilage regeneration is developed for the first time through cross-linking of 4-arm poly(ethylene glycol)-vinyl sulfone (PEG-VS) and specific matrix metalloproteinase (MMP) 13-sensitive peptides. The hydrogel exhibits diagnostic logic to identify the pathological cue MMP13 and accordingly determine drug release kinetics in an inflammatory microenvironment. Additionally, multiphase therapeutic ability is designed to program different cargo release behaviors to match the inflammation-chondrogenesis cascade for better cartilage regeneration. Here, it is first proposed that MMP13 is a suitable diagnostic biomarker to modulate the inflammatory microenvironment in the early stage of cartilage injury. In vitro and in vivo studies show that the hydrogel has good injectability, on-demand anti-inflammation, and immunomodulation capabilities. Ultimately, loaded with multiple therapeutic factors, the hydrogel shows both microenvironmental modulation and chondrogenesis therapeutic ability, resulting in satisfactory hyaline cartilage regeneration. This study provides critical insight into the design and biological mechanism of both diagnostic and therapeutic ability-based cartilage tissue engineering strategies.
研究领域:
组织工程
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生物材料
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再生医学
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生物医学工程
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骨科
✓ 已验证
DOI
高影响因子
TISSUE & CELL
·
2023
·
IF 2.6
Yujun Zhao,Xiaotie Wang,Keke Nie
Background Osteoarthritis is a main cause of deformity in aging people. The chondrogenesis of human adipose-derived stem cells (hADSCs) has a positive effect on the cure of osteoarthritis. However, the regulatory mechanism of hADSC chondrogenesis still needs further exploration. This research investigates the role of interferon regulatory factor 1 (IRF1) in the chondrogenesis of hADSCs. Methods hADSCs were purchased and cultured. The interaction between IRF1 and hypoxia inducible lipid droplet associated (HILPDA) was predicted by bioinformatics analysis, and verified through dual-luciferase reporter and chromatin immunoprecipitation assays. The expressions of IRF1 and HILPDA in osteoarthritis cartilage samples were measured through qRT-PCR. After hADSCs were transfected or further induced for chondrogenesis, the chondrogenesis was visualized by Alcian blue staining, and the expressions of IRF1, HILPDA and chondrogenesis-related factors (SOX9, Aggrecan , COL2A1, MMP13, MMP3) were determined through qRT-PCR or Western blot . Results HILPDA bound to IRF1 in hADSCs. IRF1 and HILPDA levels were up-regulated during the chondrogenesis of hADSCs. Overexpressions of IRF1 and HILPDA promoted the chondrogenesis of hADSCs with the up-regulation of SOX9 , Aggrecan and COL2A1 and the down-regulation of MMP13 and MMP3 ; however, IRF1 silencing generated the opposite effects. Besides, HILPDA overexpression reversed the effects of IRF1 silencing on inhibiting chondrogenesis of hADSCs and regulating the expressions of chondrogenesis-related factors. Conclusion IRF1 promotes the chondrogenesis of hADSCs through up-regulating HILPDA level, providing novel biomarkers for treating osteoarthritis.
研究领域:
干细胞生物学
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骨科
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Li-Shuang Hou,Jin-Yi Zhao,Yan-Qi Zou,Yao-Wen Zhang,Jie-Hua Xing,Wei He,Si-Yuan Zhou,Bang-Le Zhang
Liver fibrosis is a pathological process of abnormal proliferation of extracellular matrix (ECM) in liver. The activation of hepatic stellate cells (HSCs) is the main driving factor to form ECM in liver fibrosis. Deposition of ECM could further reactivate HSCs to result in a vicious cycle to promote the deterioration of liver fibrosis. It is of great significance to explore effective synergistic strategies not only inhibiting HSCs activation but also degrading the already formed ECM for the treatment of liver fibrosis. The targeted and stimuli-responsive gene/drug synergistic therapeutic system HCQ/p Mmp13 @PR based on the plasmid of pcDNA3.1- Mmp13 (p Mmp13 ) and hydroxychloroquine (HCQ) was constructed by using gene vector polyethyleneimine-polyethylene glycol-retinol (PR) modified with retinol (ROL) for targeting aHSCs. HCQ/p Mmp13 @PR had good stability, gene protection ability, targeting ability to aHSCs and biosafety. HCQ/p Mmp13 @PR had the characteristic of stimuli-responsive release of HCQ and p Mmp13 by intracellular high glutathione (GSH) environment, thus producing effective synergistic anti-liver fibrosis performance. The immunofluorescence, immunohistochemistry, western blot and flow cytometry experiments confirmed the synergistic therapeutic effect in vitro and in vivo. HCQ/p Mmp13 @PR could not only inhibit the autophagy to reduce the activation of HSCs, but also promote the expression of matrix metalloproteinase-13 (MMP-13) to degrade ECM to improve liver fibrosis. HCQ/p Mmp13 @PR co-delivery system has a good synergistic effect on the treatment of liver fibrosis, which provides the clinical experimental basis for the development of anti-liver fibrosis drugs.
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DOI
高影响因子
CYTOTECHNOLOGY
·
2021
·Vol. 73
·期 5
·715-726
·
IF 2.058
Xu Haiqiao,Lin Shibang,Huang Haizhou
CCL22, which could induce chondrocyte apoptosis, was identified to be overexpressed in damaged cartilage. This study was conducted with the aim of investigating the effects of CCL22 interference on chondrocyte injury. The osteoarthritis model was established by stimulating chondrocytes with LPS. The expressions of CCL22, CCR4, matrix metallopeptidase (MMP) 3, MMP9, MMP13, (a disintegrin and metalloproteinase with thrombospondin-like motifs) ADAMTS-4, collagen II and inflammatory cytokines were measured using quantitative reverse transcription PCR (RT-qPCR) and western blot. Besides, immunoprecipitation (IP) was employed to verify the binding of CCL22 and CCR4. After CCR4 was overexpressed, cell viability was observed using Cell Counting Kit-8 (CCK-8). Additionally, cell apoptosis as well as its related proteins was detected by TUNEL and western blot, respectively. ng What’s more, glycosaminoglycan (GAG) level was detected using GAG kits. CCL22 and CCR4 expression increased noticeably in LPS-stimulated ATDC5 chondrocytes. CCL22 inhibition could suppress the expression of CCR4 in LPS-induced ATDC5 cells. Likewise, CCL22 inhibition could revive the activation of LPS-induced ATDC5 cells by regulating CCR4. In addition, CCL22 knockdown alleviated inflammatory response and cell apoptosis through CCR4. Furthermore, the cartilage degradation of ADTC5 cells could be relieved by CCL22 silence via regulating CCR4. CCL22/CCR4 expression was increased in osteoarthritic cartilage injury and participated in the inflammation and cartilage degradation of chondrocytes.
研究领域:
风湿病学
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细胞生物学
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分子生物学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2020
·Vol. 8
·期 15
·3016-3027
·
IF 5.344
Qian Wu,Kaipeng Wang,Xichao Wang,Guohai Liang,Jinming Li
Controlling and detecting cell differentiation in human mesenchymal stem cells (hMSCs) for regenerative medicine remain challenging at present. Here, we developed multifunctional gold nanoparticles (AuNPs) to control and detect osteogenic differentiation in human mesenchymal stem cells (hMSCs) in real-time. The polyethyleneimine (PEI) capped AuNPs (Au-PEI) were synthesized first and were then conjugated with a matrix metalloproteinase 13 (MMP13)-sensitive peptide-FITC group (EGPLGVRGKG-FITC) to obtain multifunctional AuNPs (AuNP-PEI-peptide-FITC). AuNP-PEI-peptide-FITC could bind siRNA with PEI by electrostatic interactions to form the AuNP-PEI-peptide-FITC/siRNA nanocomplexes, allowing efficient siRNA delivery in hMSCs. The adipogenic-related gene peroxisome proliferator-activated receptor γ (PPARγ) was targeted for silencing by the AuNP-PEI-peptide-FITC/siRNA nanocomplexes to control osteogenic differentiation in hMSCs. After demonstrating that the AuNP nanocomplexes could control cell differentiation, the versatility of this tool was illustrated by showing that it can be used as a nanoprobe for real time detection of the osteogenic differentiation of hMSCs. This was done by measuring the activity of the MMP13 enzyme (produced during osteogenic differentiation) through the recovery of FITC fluorescence. This multifunctional AuNP showed a robust new methodology for controlling cell fate and simultaneously detecting cell differentiation in real-time for hMSCs, which is promising for multiple applications in regenerative medicine.
研究领域:
纳米技术
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干细胞生物学
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再生医学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CURRENT MEDICINAL CHEMISTRY
·
2024
·
IF 3.5
Shang JingJing,Xiong Chenwei,Jiang Wei,Yu Zhentang,Zhang Junjie,Zhang Yi,Han Long,Miao Kaisong,Yu Changlin,Huang Yong,Zhou Xindie
Background: Osteoarthritis (OA) is a chronic joint disease, usually accompanied by degeneration
of the articular cartilage, fibrosis, bone hyperplasia around the joint, and damage to the
entire articular surface. Gossypol is a natural phenolic compound isolated from the seed of cotton
plants, and gossypol acetic acid (GAA) is a medicinal form of Gossypol. Recently, various biological
activities of GAA, including anti-inflammatory and anti-tumor effects, have been widely reported.
However, its effect on chondrocytes in OA has yet to be determined.
Methods: In this study, we investigated the effect of GAA on ferroptosis in OA chondrocytes. The
effect of GAA on the cell viability and cytotoxicity of chondrocytes in rat cells was investigated
using CCK8. Western blotting, Reverse-transcription PCR (RT-PCR), and immunofluorescence
staining were used to elucidate the molecular mechanisms and signaling pathways of GAA inhibition
of ferroptosis in OA chondrocytes. The effect of GAA on reactive oxygen species (ROS) production
and lipid peroxidation levels in chondrocytes was examined using dihydroethidium (DHE)
staining and fluorescent dye BODIPY581/591 C11. in vivo, micro-CT imaging, hematoxylin
and eosin staining, Safranin O-Fast staining, and immunohistochemistry were performed to evaluate
the effects of GAA on OA cartilage.
Results: The results showed that GAA treatment regulated the expression of chondrocyte extracellular
matrix (ECM) related factors, including ADAMTS5, MMP13, SOX9, Aggrecan, and
COL1A2 and reduced the ROS and lipid peroxidation levels. Besides, Erastin could reverse the effects
of GAA on chondrocytes. Similar to GAA, 5-AZA caused the reduction of ROS and lipid
peroxidation levels and reversed the effect of IL-1β on the expression of ECM-related factors in
OA chondrocytes. The above results clarified that GAA alleviated the ferroptosis of chondrocytes
in OA by inhibiting GPX4 methylation.
Conclusion: Our findings revealed that GAA might be developed as a drug for treating OA clinically.
研究领域:
药理学
·
骨科
·
细胞生物学
·
生物化学
✓ 已验证
DOI
PubMed
高影响因子
Food & Function
·
2020
·Vol. 11
·期 12
·10852-10863
·
IF 4.171
Mingbao Gu,Jie Jin,Chenghao Ren,Ximiao Chen,Weiyang Gao,Xiangyang Wang,Yaosen Wu,Naifeng Tian,Zongyou Pan,Aimin Wu,Yifei Zhou,Xiaolei Zhang
As an ordinary joint vestigial disease, osteoarthritis (OA) contributes to a considerable proportion of disability cases worldwide. Inflammation, as the main pathological factor, mediates the occurrence and development of OA. Akebia Saponin D (ASD), also known as Asperosaponin VI, is one of the active components extracted from Dipsaci Radix and is rich in Dipsacus loose tea. It has shown sound therapeutic effects on various diseases; nevertheless, its role in OA therapy is not completely understood. This study demonstrated the anti-inflammatory activity of ASD in OA through a series of in vivo and in vitro experiments. In vitro experiments revealed that ASD might prohibit the production of inflammatory mediators in IL-1β treated chondrocytes such as COX-2, iNOS, NO, PGE2, IL-6, and TNF-α. Meanwhile, it may also inhibit the production of ADAMTS-5 and MMP13 and promote the production of Aggrecan and Collagen II. The mechanism study demonstrated that ASD exerted an anti-inflammatory effect by activating the NRF2 target, upregulating the expression of HO-1, and preventing P65 from binding to DNA. In vivo experiments demonstrated that ASD might improve the progression of OA in a DMM mouse model. These research results provide evidence for the potential application of ASD in OA therapy.
研究领域:
药理学
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风湿病学
·
炎症研究
·
骨科
✓ 已验证
DOI
PubMed
高影响因子
BMC Chemistry
·
2019
·Vol. 13
·期 1
·1-13
·
IF 0
He Yu-Kun,Cen Xiao-tong,Liu Shuang-shuang,Lu Hua-ding,He Chun-nian
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 EC50 and plot a dose–response 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.Conclusion sTen 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.
研究领域:
药理学
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风湿病学
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传统中药
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细胞生物学
·
生物化学
✓ 已验证
DOI
PubMed
LIFE SCIENCES
·
2024
·
IF 5.2
Min Qiu,Liangyan Cheng,Jianbo Xu,Minwei Jin,Wenhua Yuan,Qinwen Ge,Kaiao Zou,Jiali Chen,Yuliang Huang,Ju Li,Liming Zhu,Bing Xu,Chunchun Zhang,Hongting Jin,Pinger Wang
Aims The main pathological features of osteoarthritis (OA) include the degeneration of articular cartilage and a decrease in matrix synthesis. Chondrocytes, which contribute to matrix synthesis, play a crucial role in the development of OA. Liquiritin, an effective ingredient extracted from Glycyrrhiza uralensis Fisch., has been used for over 1000 years to treat OA. This study aims to investigate the impact of liquiritin on OA and its underlying mechanism. Materials and methods Gait and hot plate tests assessed mouse behavior, while Micro-CT and ABH/OG staining observed joint morphological changes. The TUNEL kit detected chondrocyte apoptosis. Western blot and immunofluorescence techniques determined the expression levels of cartilage metabolism markers COL2 and MMP13, as well as apoptosis markers caspase3, bcl2, P53, and PUMA. KEGG analysis and molecular docking technology were used to verify the relationship between liquiritin and P53. Key findings Liquiritin alleviated pain sensitivity and improved gait impairment in OA mice. Additionally, we found that liquiritin could increase COL2 levels and decrease MMP13 levels both in vivo and in vitro. Importantly, liquiritin reduced chondrocyte apoptosis induced by OA, through decreased expression of caspase3 expression and increased expression of bcl2 expression. Molecular docking revealed a strong binding affinity between liquiritin and P53. Both in vivo and in vitro studies demonstrated that liquiritin suppressed the expression of P53 and PUMA in cartilage. Significance This indicated that liquiritin may alleviate OA progression by inhibiting the P53/PUMA signaling pathway, suggesting that liquiritin is a potential strategy for the treatment of OA.
研究领域:
药理学
·
骨科
·
细胞生物学
·
分子生物学
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生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
Journal of Orthopaedic Surgery and Research
·
2022
·Vol. 17
·期 1
·1-10
·
IF 2.677
Bin-bin Zhang,Da-wa Zha Xi,Chao Li,Lan-tao Zhang,Tao Wu,Chuan Lu,Chao-zheng Liu,De-chun Li,Chang Feng,Shu-qing Wei,Zu-nan Dong,Xian-wei Pei,Zhang Zhi-xia,Ke-wen Li
Background Bone marrow mesenchymal stem cells have always been a heated research topic in bone tissue regeneration and repair because of their self-renewal and multi-differentiation potential. A large number of studies have been focused on finding the inducing factors that will promote the osteogenic differentiation of bone marrow mesenchymal stem cells. Previous studies have shown that macrophage exosomes or miRNA-26a-5p can make it work, but the function of this kind of substance on cell osteogenic differentiation has not been public.Methods M2 macrophages are obtained from IL-4 polarized bone marrow-derived macrophages. Exosomes were isolated from the supernatant of M2 macrophages and identified via transmission electron microscopy (TEM), western blotting, and DLS. Chondrogenic differentiation potential was detected by Alcian blue staining. Oil red O staining was used to detect the potential for lipogenic differentiation. And MTT would detect the proliferative capacity of cells. Western blot was performed to detect differential expression of osteogenic differentiation-related proteins.Results The results showed that M2 macrophage exosomes will promote bone differentiation and at the same time inhibit lipid differentiation. In addition, M2 macrophage-derived exosomes have the function of promoting the expression of SOX and Aggrecan suppressing the level of MMP13. The exosome inhibitor GW4689 suppresses miRNA-26a-5p in M2 macrophage exosomes, and the treated exosomes do not play an important role in promoting bone differentiation. Moreover, miRNA-26a-5p can enable to promote bone differentiation and inhibit lipid differentiation. miRNA-26a-5p can promote the expression of ALP (alkaline phosphatase), RUNX-2 (Runt-related transcription factor 2), OPN(osteopontin), and Col-2(collagen type II). Therefore, it is speculated that exosomal miRNA-26a-5p is indispensable in osteogenic differentiation.Conclusion sThe present study indicated that M2 macrophage exosomes carrying miRNA-26a-5p can induce osteogenic differentiation of bone marrow-derived stem cells to inhibit lipogenic differentiation, and miRNA-26a-5p will also promote the expression of osteogenic differentiation-related proteins ALP, RUNX-2, OPN, and Col-2.
研究领域:
干细胞生物学
·
骨组织工程
·
外泌体研究
·
微小RNA功能
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2024
·Vol. 28
·期 23
·e70271
·
IF 4.3
Zongrui Yang,Yuanyuan Feng,Mingcai Zhang,Yongming Liu,Yizhe Xiong,Xiang Wang,Ying Shi,Bo Chen,Zhengming Wang,Haiya Ge,Hongsheng Zhan,Zhibi Shen,Guoqing Du
HBP-A is the main active component of a traditional Chinese medicine Huaizhen Yanggan Capsule, for the remarkable treatment of knee osteoarthritis (KOA). This study aimed to elucidate the ameliorative effect of HBP-A on meniscus hypertrophy and mineralisation in KOA and the molecular mechanism of its action. An Hartley guinea pig model of KOA that underwent anterior cruciate ligament transection (ACLT) and a model of rat primary meniscus fibrochondrocytes (PMFs) were used to investigate the ameliorative effect of HBP-A on meniscal hypertrophy and calcification and its signal transduction mechanism of action. The results show that Guinea pig's meniscus width, as well as the area of meniscus calcification and meniscus and articular cartilage injury score, were significantly reduced in the HBP-A intervention group compared to the ACLT group. The expression levels of mtrix metalloproteinase 13 (MMP13), runt-related transcription factor 2 (Runx2), Indian hedgehog (Ihh), alkaline phosphatase (ALP), and ankylosis homologue (ANKH) at the protein and gene level significantly decreased in the HBP-A intervention group compared to the ACLT group. In vitro study, apoptosis, hypertrophy, and calcification of rat PMFs after 10% stretch force were significantly improved with HBP-A intervention. Western blot and RT-qPCR showed that hypertrophy, calcification, and p38 MAPK signalling pathway-related markers of PMFs were incredibly depressed in the HBP-A intervention group compared to the 10% stretch force group. In conclusion, HBP-A can slow down meniscus hypertrophy and mineralisation induced by abnormal mechanical loading, and its mechanism of action may be through the p38-MAPK signalling pathway.
研究领域:
药理学
·
骨科
·
分子生物学
·
传统中药
✓ 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）