COLLOIDS AND SURFACES B-BIOINTERFACES
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2024
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IF 5.4
Chen Liu,Wanchun Du,Liang Zhang,Jiacheng Wang
Curcumin (Cur) is a natural polyphenol that is one of the most valuable natural products. However, its use as a functional food is limited by low water solubility, chemical instability and poor bioavailability. In this study, a supramolecular co-assembly strategy was used to construct an oleanolic acid-curcumin (OLA-Cur) co-assembly composite nano-slow-release treatment system. As a co-assembled compound, OLA is a widely present pentacyclic triterpenoid compound with multiple biological activities in the plant kingdom, which is expected to jointly alleviate the damaging effects of papain-induced mouse osteoarthritis model. The OLA-Cur NPs shows the solid core-shell structure, which can effectively improve the water solubility of Cur and OLA, and has good stability and sustained release characteristics. The analysis results show that the two compounds are mainly assembled through hydrogen bonding interactions, hydrophobic interactions, and π - π stacking interactions. The OLA-Cur NPs can inhibit the release of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β induced by LPS in RAW264.7 mouse macrophages, promote the secretion of anti-inflammatory cytokine IL-10, and improve the oxidative stress index of hydrogen peroxide induced human rheumatoid arthritis synovial fibroblasts. In addition, it has a certain improvement effect on cartilage and subchondral bone damage in mouse osteoarthritis models. These findings suggest that constructing co-assembled composite nanoparticles based on pure natural compounds may break through the limitations of a variety of important nutritional ingredients in functional foods.
研究领域:
药理学
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纳米技术
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生物医学工程
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风湿病学
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DOI
PubMed
高影响因子
Regenerative Therapy
·
2025
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IF 3.5
Shuo Qiang,Cheng Cheng,Yonghui Dong,Chao Tang,Jia Zheng,Yunke Liu
Objective More and more evidence show that diabetes is closely related to osteoarthritis (OA). However, the role and mechanism of DNA damage-inducible transcript 4 protein (DDIT4) in diabetic OA (DOA) have not been clarified. Methods We collected OA patients and non-OA subjects who underwent total knee replacement surgery, and analyzed the DDIT4 expression in synovial samples using RT-qPCR. The cell viability of fibroblast-like synoviocytes (FLSs) was measured by CCK-8 assay. Annexin V-FITC/PI double staining was used to detect the cell apoptosis. Scratch and Transwell assays were used to determine cell migration and invasion, respectively. Results The levels of cellular inflammatory factors (IL-1β, IL-6 and TNF-α), oxidative stress and glycolysis related indicators were detected by using kits. Western blot was used to determine the expression of DDIT4, Aggrecan, COL3A1, MMP3, MMP13, HK2, PFKP and PKM2 in FLSs or ATDC5 cells. The results showed that the expression level of DDIT4 was significantly reduced in the synovial samples of OA patients and primary FLSs. Functional studies showed that DDIT4 overexpression inhibited the overactivation, migration, and invasion of FLSs, as well as alleviated chondrocyte injury co-cultured with FLSs. Importantly, the expression of DDIT4 was down-regulated in patients with DOA and closely related to DOA. Further research found that high glucose (HG) promoted excessive activation, migration, and invasion of FLSs, and exacerbated the followed chondrocyte injury. Overexpression of DDIT4 alleviated HG-induced abnormal function of FLSs and injury to chondrocytes. Importantly, DDIT4 inhibited lactate synthesis, glucose uptake, LDH activity, extracellular acidification rate, oxygen consumption rate, and expression levels of glycolysis related protein (HK2, PFKP, PKM2) in HG-induced FLSs. And the glycolysis inhibitors (Cyto-B and 3BrPA) alleviated the injury of ATDC5 chondrocytes co-cultured with FLSs. Conclusions DDIT4 participates in HG-induced FLSs overactivation and inflammation response, as well as chondrocyte injury and OA progression by regulating glycolysis processes.
研究领域:
医学
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分子生物学
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DOI
PubMed
高影响因子
Frontiers in Immunology
·
2025
·
IF 5.9
Yao Dong,Yukun Sun,Zhipeng Zhou,Zhonghui Gai,Yihui Cai,Mei Han,Kang Zou
Aim: Osteoporosis and cartilage injury are major health concerns with limited treatment options. This study investigates the therapeutic effects of Lacticaseibacillus paracasei LC86 (LC86) on osteoporosis and cartilage damage in a zebrafish (Danio rerio) model, focusing on its modulation of the gut-bone axis and its potential mechanisms for enhancing bone health.Methods: A Dexamethasone-induced zebrafish model was used to mimic osteoporosis and cartilage injury. Zebrafish were divided into control, model, and LC86 treatment groups (3×107 CFU/mL). Bone and cartilage health were assessed using Alizarin red staining and fluorescence microscopy. Bone marker expression (sp7, runx2a, bmp2a, bmp4, and col2a1a) was quantified via qPCR. Metabolic alterations were analyzed using untargeted metabolomics, and changes in gut microbiota were examined through 16S rRNA gene sequencing.Results: LC86 treatment significantly improved bone and cartilage health, as evidenced by increased fluorescence intensity in the skull, hard bone, and cartilage (p < 0.01, p < 0.05). qPCR results showed upregulation of key bone-related genes (sp7, runx2a, bmp2a, bmp4, and col2a1a), indicating enhanced bone and cartilage structure. Metabolomics analysis revealed alterations in over 300 metabolites, with changes in anti-inflammatory and energy pathways. Gut microbiota analysis demonstrated an increase in beneficial bacteria and a decrease in pathogenic genera.Conclusions: LC86 significantly improved bone health, cartilage structure, and gut microbiota composition in a Dexamethasone-induced zebrafish model, supporting its potential as a therapeutic strategy for osteoporosis and cartilage injury via modulation of the gut-bone axis.
研究领域:
微生物学
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骨科
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分子生物学
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产品关联
DOI
PubMed
高影响因子
American Journal of Translational Research
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2018
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IF 3.061
Zhenlong Liu,Xiaoqing Hu,Peng Yang,Jiying Zhang,Chunyan Zhou,Yingfang Ao
Using a rabbit model of early-stage osteoarthritis (OA) and a sampling patients with OA, we evaluated the diagnostic utility of a fluorogenic peptide-conjugated gold nanoparticle (AuNP) probe in detecting mild cartilage injury, based on the a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4) enzyme. Synthesis of this fluorescent turn-on probe (or AU-probe) required conjugation of AuNPs with a fluorescein isothiocyanate (FITC)-modified ADAMTS-4-specific peptide (DVQEFRGVTAVIR). Synovial fluid samples were then collected from 48 adult rabbits and 100 patients for comparative testing (ADAMTS-4 ELISA and AU-probe). Rabbit and patient MRI images were also evaluated and scored. Receiver operating characteristic (ROC) curve analysis was applied to various diagnostic methods (MRI, ELISA, AU-probe, and arthroscopy), performing comparisons via logistic regression. In rabbits, the AU-probe proved nonsuperior to MRI T2 mapping and ELISA (fluorescence cutpoint > 864.965 au). In patient groups, logistic regression analysis indicated that combined AU-probe/MRI testing outperformed MRI alone, thus offsetting low MRI sensitivity and low AU-probe specificity for improved detection of mild cartilage injury (sensitivity, 82.5%; specificity, 80.0%). We have consequently confirmed the efficacy of this AU-probe, using ADAMTS-4 activity in synovial fluid to diagnose mild cartilage injury. Combining the AU-probe with conventional MRI assessment proved optimal in this setting.
研究领域:
医学
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生物技术
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诊断学
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DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
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2021
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IF 5.194
Yilong Cui,Miao Song,Bonan Xiao,Menglin Liu,Pengli Liu,Yanfei Han,Bing Shao,Yanfei Li
The problem of excessive aluminum (Al) content in food is widespread. After Al enters the body, it can cause mineral metabolism imbalance and reactive oxygen species (ROS) overproduction, which ultimately leads to bone impairment. ROS is mainly produced in mitochondria and acts on mitochondria. Mitochondrial damage is closely related to mitophagy and apoptosis . In order to clarify whether ROS-mediated mitophagy and apoptosis are involved in Al-induced femoral impairment, forty-eight male C57BL/6 N mice were exposed to AlCl 3 (179.3 mg/kg) and/or NAC (100 mg/kg) for 90 days. Our results showed that NAC inhibited the mitophagy and apoptosis, and alleviated growth inhibition, mineral metabolism imbalance, structural damage, decreased bone mineral density and decreased bone formation factor expressions in the femora of Al-treated mice. These results suggest that ROS-mediated mitophagy and apoptosis are involved in Al-induced femoral impairment in mice, exogenous ROS clearance is a potential strategy for the treatment of Al-induced bone impairment.
研究领域:
毒理学
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骨骼生物学
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药理学
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DOI
PubMed
高影响因子
Communications Biology
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2025
·Vol. 8
·期 1
·1-14
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IF 5.1
Zhou Xiaonan,Jiang Peng,Tan Huangqi,Wang Yanfang,Bai Lunhao
Osteoarthritis (OA) is a degenerative joint disease that affects the cartilage and surrounding tissues. The transcription factor Kruppel-like family factor 9 (KLF9) has been identified as a regulator of tumorigenesis. However, its role in OA is still not fully understood. Herein, this study aimed to access the potential role and molecular mechanism by which KLF9 regulates OA development. KLF9 was upregulated in cartilage tissues of OA patients and medial meniscotibial ligament (MMTL)-induced OA rats, as well as in IL-1β-treated chondrocytes. Furthermore, knockdown of KLF9 inhibited OA-related cartilage injury, as evidenced by inhibiting chondrocyte extracellular matrix (ECM) degradation, increasing chondrocyte viability, and decreasing apoptosis. Conversely, overexpression of KLF9 had the opposite effect. The downstream mechanism of KLF9 was confirmed. KLF9 mediated the transcription of G protein-coupled receptor kinase 5 (GRK5) by directly targeting the GRK5 promoter. GRK5 knockdown eliminated the effects of KLF9 overexpression on chondrocyte dysfunction. It was also found that GRK5 combined with histone deacetylase 6 (HDAC6) and promoted HDAC6 phosphorylation. The use of the HDAC6 inhibitor TubastatinA also abolished the effects of GRK5 overexpression on chondrocyte ECM degradation and apoptosis. These results demonstrate that the KLF9-GRK5-HDAC6 axis plays a crucial role in promoting the progression of OA.
研究领域:
风湿病学
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分子生物学
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医学遗传学
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DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2025
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IF 6.1
Jiaxiang Zhang,Haitao Ma,Yongjie Yang,Liyin Liu,Dasheng Luo,Defu Yu,Tao Chen
Excessive intake of essential and toxic metals affects the pathological process of osteoporosis. At present, the effects of single forms of iron (Fe), lead (Pb) and other metals on bone injury have been widely studied. However, these metal elements usually do not exist in the environment in a separate form. They are ingested in various ways and are often found together in the human body. However, the mechanism of bone damage caused by Fe and Pb mixed exposure is still unclear at this stage. At present, the combined analysis of multi-omics is the conventional method to explore the molecular mechanism behind the disease. Therefore, we attempted to combine proteomics and metabolomics to explain the mechanism of bone damage caused by mixed Fe and Pb exposure. Differential proteins and metabolites were found to be predominantly enriched in the JAK-STAT signalling pathway, inflammatory bowel disease (IBD), and osteoclast differentiation. Combined analysis showed that Fpr2, Lifr, Lisofylline, 7-Ketocholesterol, LacCer (d18: 1/14:0) and other substances may be involved in the process of bone injury mediated by mixed metal exposure. In summary, we hypothesise that mixed exposure to Fe and Pb leads to osteoclast activation via the JAK-STAT signalling pathway in situ and indirectly via the gut-bone axis, resulting in bone damage. In general, our study potentially suggests that bone injury induced by mixed exposure of Fe and Pb may be related to osteoclast proliferation mediated by changes in inflammatory levels in vivo .
研究领域:
分子生物学
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毒理学
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骨代谢研究
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产品关联
DOI
PubMed
高影响因子
Pharmacognosy Magazine
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2025
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IF 0.9
Yezhou Li,Chengjian Tang
Background and PurposeAlginate and gelatin have biocompatibility and biodegradability for drug formulations or carriers, but the roles and mechanisms in cartilage injury (CI) repair remain unclear. This research investigated the application of alginate-collagen hydrogel (ACH) in rat CI repair and its related mechanisms through in vitro and in vivo experiments.Materials and MethodsAlginate and modified collagen solutions were mixed to prepare the ACH. The obtained samples were characterized, and their sustained release properties were determined. L929 mouse fibroblasts were assigned into a blank control group (BC group, untreated), a positive control group (PC group, treated with 6.4% phenol), a negative control group (NC group, treated with tissue culture polystyrene), and an ACH group (treated with ACH). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay assessed cell viability. Meanwhile, the cytotoxicity of the ACH and its impact on cell proliferation and cell attachment capabilities were analyzed. Thirty 4-week-old specific pathogen-free Sprague-Dawley rats were randomly grouped into a chondrocyte group (chondrocytes collected and cultured), a cPAGE group (chondrocytes treated with ACH), a model group (CI model), and an mPAGE group (CI model treated with ACH). The influence of ACH on chondrocyte proliferation and type II collagen (COL-II) expression were assessed via cell counting kit 8 (CCK-8) assay and immunofluorescence staining. Furthermore, the impacts of ACH on chondrocyte tissue and COL-II expression were analyzed using Safranin O-Fast Green staining, the International Cartilage Repair Society (ICRS) score, and COL-II tissue staining. Immunoblotting was utilized to detect tumor necrosis factor alpha (TNF-α), nuclear factor kappa-B (NF-κB), matrix metalloproteinase 13 (MMP-13), and COL-II proteins in cartilage tissue.ResultsThe release rate of the constructed ACH reached over 85% within 72 h and achieved degradation equilibrium within 5 days with a weight loss rate of over 60%. L929 fibroblast culture results showed that the ACH posed no significant cytotoxicity, and cell attachment results were not obviously different from those on tissue culture plates (p < .05). MTT assay results demonstrated that the ACH exerted no adverse effects on L929 cell proliferation and growth, indicating good biocompatibility. CCK-8 and COL-II results indicated that chondrocyte proliferation in the cPAGE group was markedly higher versus that in the chondrocyte group (p < .05). Besides, animal experiments unveiled that, relative to the CI group, the mPAGE group had more chondrocytes, upregulated COL-II, and higher ICRS scores (p < .05). MMP-13, NF-κB, and TNF-α were downregulated, and COL-II was upshifted in the mPAGE group, with remarkable differences (p < .05).ConclusionACH exhibited excellent biocompatibility and low cytotoxicity, promoted cell proliferation and growth, and facilitated chondrocyte proliferation in rat CI repair, offering a valuable research foundation for CI treatment.
研究领域:
生物材料学
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组织工程学
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医学
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DOI
高影响因子
Materials Express
·
2024
·Vol. 14
·期 5
·836-843
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IF 0.7
Liu Yu’e,Liu Yuyan
Articular cartilage injuries are prevalent in track and field long jump and can affect an athlete’s health. However, current therapeutic options cannot effectively repair the damaged cartilage tissue. It is important to find alternative treatment methods that can provide better
results for injured athletes. In this study, carbon nanofibers (CNFs) were employed to enhance the properties of hyaluronic acid (HA) and develop nanocomposite hydrogel scaffolds. Bone marrow mesenchymal stem cells extracted from the joints of experimental mice were subsequently loaded onto
the CNFs-HA scaffolds and evaluated for bioactivity and repair capacity. The TEM photographs of CNFs-MA displayed an orderly arrangement of fibers. Observing the FT-IR spectral characteristics of CNFs-MA revealed a telescopic vibration peak at 1700 cm−1. CNFs-HA demonstrated
a rapid increase in cartilage damage repair score after 15 days, and at 1 month, the joint damage repair score of CNFs-HA was significantly different from that of pure HA and the untreated group. Based on the foregoing results, it can be inferred that CNFs-HA, as prepared, is biocompatible
and efficacious in treating articular cartilage tissue injury. Furthermore, this study this study provides a reliable solution for cartilage injury treatment and establishes an experimental basis for its clinical management.
研究领域:
运动医学
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生物材料学
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再生医学
✓ 已验证
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2025
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IF 5.6
Ruqi Wang,Qishu Jin,Zhaoxu Meng,Xiaodong Cao,Yihao Wu,Chen Yang,Jiandong Yuan
Oxidative stress is increasingly recognized as a key pathological driver of skeletal degeneration in diabetes, aging, trauma, and other orthopedic disorders, where excessive reactive oxygen species (ROS) compromise osteoblast and bone marrow mesenchymal stem cell (BMSC) function while promoting osteoclast activity. Natural polyphenols such as baicalein (BA) exhibit potent antioxidant effects but are hindered by poor solubility and limited stability. Here, we report a series of BA-X self-assembled nanoparticles, in which X represents osteogenic metal ions including Mg 2+ , Mn 2+ , Cu 2+ , Zn 2+ , and Sr 2+ . Among these, BA-Mn demonstrated the most robust radical-scavenging activity in DPPH, ABTS, and multiple ROS-targeted assays. BA-Mn exhibited nanoscale dimensions, uniform coordination, and excellent cytocompatibility, significantly reducing intracellular ROS and protecting H 2 O 2 -injured BMSCs. Functionally, BA-Mn restored osteogenic differentiation under oxidative stress, enhancing alkaline phosphatase activity, mineral deposition, and osteogenic gene expression. Transcriptomic analysis further revealed concurrent activation of cell cycle, PI3K-Akt, and MAPK signaling pathways, alongside suppression of ferroptosis and ROS-related carcinogenesis. Collectively, these findings establish BA-Mn as a multifunctional nanoplatform that integrates antioxidant defense with osteogenic stimulation, offering a promising therapeutic approach for oxidative stress-related bone disorders.
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2024
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IF 7.6
Lihua Feng,Yuanyuan Lang,Leke Sun,Weihong Shi,Xiangxiang Chen,Yanan Xia,Hengyi Xu,Yang Liu
Titanium dioxide nanoparticles (TiO 2 NPs) are widely used in children’s daily necessities and foods, and their health hazards to children have attracted particular attention. Childhood is a critical time for accelerated bone growth and development. Current studies revealed that TiO 2 NPs exposure causes bone damage in juvenile rats; however, the underlying mechanism is unknown. Ghrelin is a polypeptide hormone that is considered to be a candidate factor for regulating bone growth and development. In this research, 3-week-old juvenile male rats were administered 0, 100 or 200 mg/kg TiO 2 NPs and 50 μg/kg ghrelin for 4 weeks to explore the underlying mechanism of TiO 2 NPs-induced bone damage, and the protective effect of ghrelin. Our results revealed that TiO 2 NPs resulted in decreased synthesis of bone growth-related hormones, disturbed bone metabolism, and destruction of bone structure. Further mechanism studies showed that TiO 2 NPs inhibited Wnt/β-catenin pathway, reduced collagen synthesis, inhibited chondrocyte proliferation and differentiation, promoted chondrocyte apoptosis, and inhibited endochondral osteogenesis, ultimately leading to long bone longitudinal growth retardation and osteoporosis. Ghrelin alleviated the negative effects of TiO 2 NPs-induced bone growth in juvenile rats by upregulating the Wnt/β-catenin signaling pathway. This study provided a reference for the clinical treatment of growth retardation and idiopathic short stature in juvenile children caused by environmental pollutants.
研究领域:
毒理学
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内分泌学
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儿科
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骨骼生物学
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产品关联
DOI
PubMed
高影响因子
Orthopaedic Surgery
·
2021
·Vol. 13
·期 4
·1398-1407
·
IF 2.071
Ming Li,Yan-bo Xiao,Xin-tao Wang,Jin-peng Zhuang,Chang-long Zhou
Objective To explore the possible way of proline-serine–threonine phosphatase-interacting protein 2 (PSTPIP2) influencing diabetes mellitus-osteoarthritis (DM-OA) progression. Methods In vivo , eight-week-old male Sprague Dawley rats were induced with DM-OA by intraperitoneal injection of streptozotocin with high-fat diet feeding and intra-articular injection of monoiodoacetate. PSTPIP2 overexpression was achieved by intra-articular injection of lentivirus vectors. PSTPIP2 expression was verified by real-time polymerase chain reaction and Western blotting. Histological changes were examined by hematoxylin/eosin and safranin-O/fast-green staining. In vitro , rat synovial fibroblasts were induced DM-OA by stimulation of high glucose (HG) and interleukin (IL)-1β. PSTPIP2 overexpression was achieved by lentivirus infection. U0126 was added as an ERK inhibitor. Levels of tumor necrosis factor (TNF)-α, IL-6, and IL-1β were detected using enzyme-linked immunosorbent assay. Expression of matrix metalloproteinase (MMP)-3, MMP-13, aggrecanase-2 (ADAMTS-5), intercellular cell adhesion molecule (ICAM)-1, extracellular regulated protein kinase (ERK) and phospho-ERK (p-ERK) was detected by Western blotting. Results In DM-OA rats, PSTPIP2 relative messenger RNA (mRNA) level was significantly decreased compared to control rats. The protein expression was also decreased obviously. Inflammation score in synovium was dramatically increased, accompanying with increased TNF-α, IL-6, and IL-1β levels. Osteoarthritis research society international (OARSI) score in cartilage was markedly increased, along with increased MMP-3, MMP-13, ADAMTS-5, ICAM-1, ERK and p-ERK expression. In PSTPIP2-overexpressed DM-OA rats, PSTPIP2 mRNA level and protein expression was increased compared to DM-OA rats received negative-control lentivirus vectors. The inflammation score, as well as TNF-α, IL-6, and IL-1β levels were dramatically decreased. Also, the OARSI score and protein expression of MMP-3, MMP-13, ADAMTS-5, ICAM-1, ERK and p-ERK were decreased. In HG+IL-1β-treated rat synovial fibroblasts, PSTPIP2 protein expression was decreased compared to normal glucose (NG)-treated cells. Levels of TNF-α, IL-6, and IL-1β, as well as expression of MMP-3, MMP-13, ADAMTS-5, ICAM-1, ERK and p-ERK were increased. After cells were infected with PSTPIP2-overexpressed lentivirus, levels of TNF-α, IL-6, and IL-1β, and expression of MMP-3, MMP-13, ADAMTS-5, ICAM-1, ERK and p-ERK were obviously decreased compared to cells infected with NC lentivirus. In addition, ERK inhibitor U0126 treatment also decreased the TNF-α, IL-6, and IL-1βlevels and MMP-3, MMP-13, ADAMTS-5, ICAM-1, ERK and p-ERK expression in HG + IL-1β treated rat synovial fibroblasts. Conclusion Overexpression of PSTPIP2 alleviates synovial inflammation and cartilage injury during DM-OA progression via inhibiting ERK phosphorylation.
研究领域:
医学研究
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风湿病学
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糖尿病学
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DOI
PubMed
高影响因子
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