Heliyon
·
2023
·
IF 4
Jie Wang,Huiwen Hou,Yan Li,Wen Tang,Didi Gao,Zengmei Liu,XinQing Gao,Feiyan Zhao,Feng Sun,Haining Tan,Juan Wang
Oxidative stress plays a crucial role in the development of osteoporosis. In this study, it was observed that donkey bone collagen (DC) at a concentration of 500 μg/mL scavenged 17.89 % of 1,1-Diphenyl-2-picrylhydrazyl (DPPH) free radicals, indicating its antioxidant properties. Additionally, when an oxidative damage osteoblast model was created using H 2 O 2 , 100 μg/mL DC demonstrated the ability to enhance cell survival by 27.31 %. Furthermore, 50 μg/mL DC increased the intracellular differentiation marker alkaline phosphatase (ALP) level by 62.65 %. Additionally, the study revealed that DC significantly increased the expression of osteoporosis-related factors in serum and effectively restored the abnormal structure of spongy bone in mice osteoporosis model. Peptides (GGWFL, ANLGPA, and GWFK) isolated from DC through gastrointestinal digestion and subsequent enzymatic purification in vitro demonstrated the ability to safeguard osteoblasts from H 2 O 2 -induced damage by reducing intracellular reactive oxygen species (ROS). This protection resulted in enhanced cell survival and promoted osteoblast differentiation. This investigation underscores that DC can shield oxidative damage osteoblast model from oxidative stress, ameliorate osteoporosis, and enhance bone density in mice osteoporosis model. These findings suggest various DC applications in the food and medicine industries.
研究领域:
生物化学
·
医学
·
营养学
✓ 已验证
DOI
PubMed
高影响因子
Heliyon
·
2024
·
IF 3.4
Yingjie Wu,Mingxiang Fan,Shixiang Tan,Qiucheng Guo,Hegui Xu
Objective To examine and talk about the mechanism of the Huoxue Jiegu compound capsule's effects on osteoblasts and the PI3K/Akt/mTOR signal pathway in rabbits suffering from tibial fractures. Method In vitro, CCK8 was used to assess the survival rates. Alizarinred staining was used to evaluate mineralized nodules. ALP staining was used to observe the osteoblasts. qRT-PCR was used to determine the mRNA expression of the bone formation-related factors BMP-2, bFGF, and TGF-β. In vivo, three groups of nine male rabbits each were randomly assigned to three groups: the Model group, the Huoxue Jiegu compound capsule group (HXJGC group), and the inhibitor group (HXJGC+3-MA), four weeks following the intervention. HE staining was employed to examine the rabbits' bone histology. immunohistochemistry was employed to examine the relative expression of the proteins VEGF and LC3-II. Western Blot was utilized to examine the relative expression of the proteins Beclin-1, LC3-II/Ⅰ, p62, p-PI3K, p-AKT, and p-mTOR. Results Compared to the control group, the medium- and high-dose groups exhibited considerably higher survival rates ( P < 0.05), as well as enhanced cell proliferation and differentiation ( P < 0.05) and more pronounced mineralized nodules. ( P < 0.05), but the low-dose groups showed no appreciable variation. In the low, medium, and high-dose groups, there was a substantial reduction in the expression of bFGF mRNA, whereas the levels of BMP-2 and TGF-β mRNA were considerably higher than in the control group ( P < 0.05). In vivo, after four weeks of treatment, the model control group and inhibito group had a large amount of fibrous hyperplasia accompanied by bleeding and a small amount of inflammatory cell infiltration. But in the HXJGC group, new cartilage appeared, and the surface of the cartilage was smooth and flat. Beclin-1 and LC3-II/I expression in the HXJGC+3 MA group was significantly lower than in the HXJGC and Model groups ( P < 0.05). The HXJGC group showed lower p62 expression than the HXJGC+3 MA and model groups ( P < 0.05). The HXJGC group exhibited significantly reduced levels of p-PI3K, p-AKT, and p-mTOR expression in comparison to HXJGC+3 MA groups ( P < 0.05). Conclusion Rabbits with tibial fractures can be treated with HXJGC, which can control the expression of the PI3K/Akt/mTOR signal pathway. It can promote the differentiation and maturation of osteoblasts at the fracture end of rabbits, accelerate the recovery of fractures, and achieve the purpose of treating the disease.
研究领域:
医学
·
生物学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Macromolecular Science Part B-Physics
·
2024
·
IF 1.2
Jie Jiang,Jianjun Fang,Wenjuan Liu,Meimei Guo,Zhongjia Lu,Heng Tang,Yi Lan,Zhihua Zhou
Composite porous microcarriers based on demineralized bone extracellular matrix (DBECM) and chitosan (Cs) were prepared using a combined emulsion and freeze-drying method. The effects of digestion by pepsin on the DBECM properties were investigated. The morphologies and porous structure of the DBECM/Cs porous microcarriers were observed by using a scanning electron microscope (SEM). The cytocompatibility of the DBECM/Cs porous microcarriers were studied by using cell counting kit-8 (CCK-8) and calcein acetoxymethyl ester/propidium iodide (CAM/PI). DBECM was digested into small pieces with a loose porous sponge structure and the digested DBECM showed an amorphous state. The resultant DBECM/Cs porous microcarriers showed a spherical shape and an interconnective porous structure. The CCK-8 and CAM/PI analyses indicated that the DBECM/Cs porous microcarriers were non-cytotoxic and showed good biocompatibility, providing a more favorable growth environment for cells.
研究领域:
生物医学工程
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材料科学
·
组织工程
✓ 已验证
DOI
高影响因子
ADVANCED POWDER TECHNOLOGY
·
2019
·
IF 3.25
Xu Liu,Haishan Shi,Tao Yu,Changren Zhou
Nowadays, the treatment of osteoarthritis (OA), a highly prevalent joint disorder, remains a medical challenge because of the lack of understanding of its pathogenesis. In this work, we developed an alternative strategy of OA treatment using magnesium-based materials as potential therapeutic agent towards subchondral bone remodeling. We selected deer antlers as the animal model where calcification behaviors could provide interesting references for the rapid and reproducible endochondral bone growth. Extremely high content of Mg was detected in the antler, which was able to affect the evolutions of biological apatite. Herein, octacalcium phosphate (OCP) and amorphous calcium phosphate (ACP), which are critically involved in the calcification process, were respectively synthesized under the Mg-containing conditions to understand the role of Mg in the evolution of biological apatite. Results showed that the substitution of Mg 2+ at lower contents stabilized OCP and ACP, while higher contents of Mg inhibited the formation of both phases. The size of both calcium phosphates was also altered significantly by the addition of Mg. The results of cell culture indicated that excess Mg notably accelerated the secretion of extracellular matrix and inhibited the mineralization of chondrocyte matrix. Hence, utilization of Mg-based materials in subchondral bone was supposed to provide a potential therapeutic approach to treat the OA by inhibiting subchondral of ossification process.
研究领域:
生物材料
·
骨科
·
生物矿化
✓ 已验证
产品关联
DOI
高影响因子
Cells
·
2024
·Vol. 13
·期 23
·2028
·
IF 5.1
Ying Wang,Xueru Wang,Kaijin Wang,Weiwei Qin,Ning Li
Postmenopausal osteoporosis (PMOP) is a bone disease characterized by bone thinning and an increased risk of fractures due to estrogen deficiency. Current PMOP therapies often result in adverse side effects. The traditional medicinal plantCurculigo capitulatais commonly used to strengthen bones and support kidney function, but its role in treating PMOP is not well understood. This study aims to investigate the therapeutic effects of the total extract ofCurculigo capitulata(Eocc) on PMOP and to explore the underlying mechanisms. The major components of the extract were identified using HPLC. Transcriptomics was employed to predict potential targets. An osteogenic differentiation model of MC3T3-E1 cells was used in vitro. The osteogenic potential of the Eocc was assessed through CCK-8 cell viability assays, alkaline phosphatase (ALP) staining, Alizarin Red staining, Western blotting, and qPCR. MCF-7 and HEK-293 cells were utilized to evaluate the estrogen-like activity of Eocc. Apoptosis rates were detected by flow cytometry. In vivo, a bilateral ovariectomized mouse model of PMOP was used to further validate the in vitro findings through histopathological analysis and WB results. The results demonstrated that the Eocc promoted the proliferation of MC3T3-E1 cells, increased ALP activity, and stimulated the formation of osteogenic mineralized nodules. It also upregulated the expression of osteogenic markers (Runx2, OCN, OPN, and BSP) at both the protein and mRNA levels. The Eocc induced the activation of ERα both in vitro and in vivo, initiating the Src/PI3K/AKT signaling pathway, leading to the phosphorylation of GSK3β and subsequent osteogenesis. The activation of this pathway also stimulated the phosphorylation of mTOR and p70S6K while downregulating cleaved caspase-3 and caspase-9. Additionally, the Eocc reduced apoptosis during osteogenic differentiation and promoted cell proliferation. These findings suggest that the Eocc facilitates osteoblast proliferation and differentiation, improving bone integrity in PMOP mice, and may represent a promising therapeutic candidate for managing PMOP.
研究领域:
药理学
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骨生物学
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分子生物学
·
转化医学
✓ 已验证
DOI
PubMed
高影响因子
Materials Today Bio
·
2024
·
IF 8.7
Dongze Wu,Shuhui Yang,Zhe Gong,Xinxin Zhu,Juncong Hong,Haitao Wang,Wenbin Xu,Juncheng Lai,Xiumei Wang,Jiye Lu,Xiangqian Fang,Guoqiang Jiang,Jinjin Zhu
Osteoarthritis (OA) is characterized by symptoms such as abnormal lubrication function of synovial fluid and heightened friction on the cartilage surface in its early stages, prior to evident cartilage damage. Current early intervention strategies employing lubricated hydrogels to shield cartilage from friction often overlook the significance of hydrogel-cartilage adhesion and enhancement of the cartilage extracellular matrix (ECM). Herein, we constructed a hydrogel based on dihydrazide-modified hyaluronic acid (HA) (AHA) and catechol-conjugated aldehyde-modified HA (CHA), which not only adheres to the cartilage surface as an effective lubricant but also improves the extracellular environment of chondrocytes in OA. Material characterization experiments on AHA/CHA hydrogels with varying concentrations validated their exceptional self-healing capabilities, superior injectability and viscoelasticity, sustained adhesion strength to cartilage, and a low friction coefficient. Chondrocytes exhibited robust adhesion and proliferation on the AHA/CHA hydrogel surface, with the upregulation of cartilage matrix protein expression. Intra-articular injection of AHA/CHA hydrogels was performed following destabilization of the medial meniscus (DMM) surgery in mice to assess its protective effect on cartilage. The AHA/CHA hydrogel effectively attenuated the degree of cartilage wear, facilitated chondrocytes' anabolic metabolism, and restored the ECM of cartilage. Therefore, the AHA/CHA hydrogel emerges as a promising therapeutic approach in clinical practices of OA treatment.
研究领域:
生物医学工程
·
骨科
·
组织工程
·
再生医学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers of Materials Science
·
2024
·Vol. 18
·期 3
·1-15
·
IF 2.5
Cui Zeqin,Hu Qifeng,Wang Jianzhong,Zhou Lei,Hao Xiaohu,Wang Wenxian,Li Weiguo,Cheng Weili,Chang Cheng
Zinc-based composites represent promising materials for orthopedic implants owing to their adjustable degradation rates and excellent biocompatibility. In this study, a series of Zn–10Mg– x HA ( x = 0–5 wt.%) composites with the core–shell structure were prepared through spark plasma sintering, and their microstructural, mechanical, and in vitro properties were systematically evaluated. Results showed that the doped hydroxyapatite (HA) is concentrated at the outer edge of the MgZn 2 shell layer. The compression strength of the Zn–10Mg–HA composite gradually decreased with the increase of the HA content, while its corrosion rate decreased initially and then increased. The corrosion resistance of the composite with the addition of 1 wt.% HA was improved compared to that of Zn–10Mg–0HA. However, the further increase of the HA content beyond 1 wt.% resulted in a faster degradation of the composite. Moreover, the Zn–10Mg–1HA composite significantly enhanced the activity of MC3T3-E1 osteoblasts. Based on such findings, it is revealed that the composite containing 1 wt.% HA exhibits superior overall properties and is anticipated to serve as a promising candidate for bone implant materials.
研究领域:
材料科学
·
生物材料
·
骨科
✓ 已验证
DOI
高影响因子
MOLECULAR THERAPY
·
2024
·
IF 12.1
Liqing Ke,Qifei He,Jing Qu,Xiyue Wang,Kaibo Li,Xun Gong,Lan Li,Jiake Xu,Qiuliyang Yu,Hao Yu,Xuefei Lin,Jian Li,Nguan Soon Tan,Wei Sun,Liang Li,Peng Zhang,Wenxiang Cheng
Despite recent advances, rheumatoid arthritis (RA) patients remain refractory to therapy. Dysregulated overproduction of angiopoietin-like protein 4 (ANGPTL4) is thought to contribute to the disease development. ANGPTL4 was initially identified as a regulator of lipid metabolism, which is hydrolyzed to N-terminal and C-terminal (cANGPTL4) fragments in vivo . cANGPTL4 is involved in several non-lipid-related processes, including angiogenesis and inflammation. This study revealed that the level of ANGPTL4 was markedly elevated in the sera and synovial tissues from patients with RA versus controls. The administration of a neutralizing antibody against cANGPTL4 (anti-cANGPTL4 Ab) resulted in the inhibition of inflammatory processes and bone loss in animal models of collagen-induced arthritis and adjuvant-induced arthritis (AIA). Transcriptomic and proteomic profiling of synovial tissues from an AIA model indicated that the anti-cANGPTL4 Ab inhibited fibroblast-like synoviocyte (FLS) immigration and inflammatory-induced osteoclastogenesis. Mechanistically, the anti-cANGPTL4 Ab has been shown to inhibit TNF-α-induced inflammatory cascades in RA-FLS through the sirtuin 1/nuclear factor-κB signaling pathway. Moreover, the anti-cANGPTL4 Ab was found to block FLS invasion- and immigration-induced osteoclast activation. Collectively, these findings identify ANGPTL4 as a prospective biomarker for the diagnosis of RA, and targeting cANGPTL4 should represent a potential therapeutic strategy.
研究领域:
免疫学
·
风湿病学
·
分子生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
Aggregate
·
2024
·
IF 13.9
Shuqi Wu,Fang Nan,Kewen Zhang,Wan Hao,Di Shi,Yang Li,Wei Deng,Nur Jarhen,Kaixuan Li,Yunyun Xiao,Jun Li,Xiao Lin
Osteoarthritis (OA) is associated with metabolic imbalance of articular cartilage and an increase of intracellular reactive oxygen species (ROS). Synergistic therapy based on the codelivery of ROS scavengers and antisense oligonucleotides (ASO) into chondrocytes has the potential to effectively treat OA. Here, we developed a novel biocompatible metal-organic framework (MOF)-encapsulated nanozyme/ASO delivery platform (miR/IrO 2 @ZIF-8) for OA treatment. IrO 2 nanoparticles with the catalytic activities of superoxide dismutase/catalase were synthesized using a hydrothermal method, resulting in excellent ROS scavenging performance. IrO 2 was further loaded into zeolitic imidazolate framework-8 (ZIF-8) to maintain its catalytic efficacy and regulate its size, surface charge, and biocompatibility to enhance the therapeutic effect of the platform. As an effective ASO delivery carrier, the synthesized IrO 2 @ZIF-8 exhibited high antagomiR-181a loading and lysosomal escape capacity, enabling it to rebalance cartilage metabolism. In vitro experiments showed that miR/IrO 2 @ZIF-8 could restore ROS levels, mitochondrial membrane potential, and lipid peroxidation in chondrocytes. At the same time, the expression levels of proinflammatory markers (IL-1β, IL-6, and COX-2) as well as the extracellular matrix degrading enzymes (ADAMTS-5 and MMP13) were downregulated, indicating effective antioxidant, anti-inflammatory, and anticartilage degradation effects. Notably, miR/IrO 2 @ZIF-8 was able to deliver IrO 2 nanoparticles and antagomiR-181a to the cartilage tissue at a depth of up to 1.5 mm, thus solving the problems of poor permeability and difficult retention of drugs in cartilage tissue. This further improves the synergistic therapeutic effect on OA by inhibiting cartilage degradation. The combination of MOF-encapsulated IrO 2 nanozymes with antagomiR-181a has an excellent therapeutic effect on OA, offering a promising translational medicine paradigm.
研究领域:
纳米技术
·
药学
·
生物医学工程
·
骨科
·
材料科学
✓ 已验证
DOI
高影响因子
RSC Advances
·
2024
·Vol. 14
·期 31
·22420-22433
·
IF 3.9
Chunyan Tian,Kun Li,Fuhuan Chu,Qiujiang Wei,Shiqi Xu,Linhui Qiang,Xinrui Gou
Traditional bone tissue engineering techniques require the extraction and proliferation of seed cells, followed by prolonged in vitro culture to form bone tissue constructs. In contrast, in situ mineralization bone tissue engineering utilizes alkaline phosphatase within the body's microenvironment to induce scaffold mineralization. This approach promotes further proliferation and differentiation of osteoblasts and the formation of bone tissue constructs, thereby simplifying the traditional bone tissue engineering process. This study uses electrospinning technology to prepare a novel biologically active scaffold for bone tissue engineering using poly(lactic-co-glycolic acid) (PLGA) and calcium glycerophosphate. The morphology and composition of the scaffolds were characterized using SEM, EDS, and XRD, revealing well-defined fibrous structures and the successful incorporation of calcium glycerophosphate into the PLGA fibers. In vitro simulation of the bone microenvironment using alkaline phosphatase effectively catalyzed the in situ mineralization of calcium glycerophosphate within the scaffold. SEM observations showed substantial mineral aggregation on the surface of the fibrous membranes, and XRD characterization confirmed that the diffraction peaks of the minerals correspond to hydroxyapatite. The cytotoxicity, cell proliferation, and osteogenic differentiation assessments on MC3T3-E1 pre-osteoblasts cultured on the prepared scaffolds indicate that the scaffolds are non-toxic to cells and possess good osteogenic differentiation ability, enabling in situ mineralization. This suggests that the scaffolds have broad prospects for application in bone defect repair.
研究领域:
生物医学工程
·
材料科学
·
组织工程
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
CELL BIOLOGY INTERNATIONAL
·
2024
·
IF 3.3
Yuhua Zhang,Hanping Shi
This study explores the potential role and mechanism of Ginsenoside Rb3 (Rb3) in modulating osteoclastogenesis induced by human periodontal ligament fibroblasts (hPLFs) within the periodontitis microenvironment. We investigated the anti-inflammatory effects of Rb3 on hPLFs stimulated with Porphyromonas gingivalis lipopolysaccharide ( P.g -LPS) utilizing quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay techniques. Moreover, the functional role of Rb3 in hPLFs-induced osteoclast formation was assessed by treating human bone marrow-derived macrophages (hBMMs) with conditioned medium from hPLFs, followed by analyses through qPCR, western blot analysis, and staining for tartrate-resistant acid phosphatase (TRAP) and phalloidin. The impact of Rb3 on the activation of the STAT3 signaling pathway was determined via western blot analysis. Results indicated that Rb3 treatment significantly suppressed the upregulation of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, MCP-1, and IL-18) at both gene and protein levels in hPLFs induced by P.g -LPS. Furthermore, conditioned medium from Rb3 plus P.g -LPS treated hPLFs notably decreased the number of TRAP-positive cells, actin ring formations, and the expression of osteoclast marker genes (including CTSK, NFATC1, and ACP5). Rb3 also inhibited the P.g -LPS-induced activation of the STAT3 pathway, with the activation of STAT3 partially reversing the effects of Rb3 on inflammation and osteoclast differentiation. Collectively, Rb3 ameliorates inflammation in P.g -LPS-stimulated hPLFs and reduces hPLFs-induced osteoclastogenesis by inhibiting the STAT3 signaling pathway, suggesting its potential as a therapeutic agent for periodontitis.
研究领域:
牙科学
·
药理学
·
免疫学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
ALTERNATIVE THERAPIES IN HEALTH AND MEDICINE
·
2024
·
IF 1.9
Guo Z,Qin Y,Li Y,Tang P
Objective Given the crucial role of the PI3K/Akt signaling pathway in chondrocyte survival and inflammation in osteoarthritis (OA), this study aimed to investigate the effects of Gu Bi Tang on chondrocyte proliferation, apoptosis, and inflammatory factor expression in a rat model of OA, with a focus on the PI3K/Akt signaling pathway. Methods Forty-five specific pathogen-free (SPF) C57 mice were randomly divided into three groups: the model group (Group A), the Gu Bi Tang group (Group B), and the Amfenac group (Group C), with 15 rats in each group. All 45 rats underwent anterior cruciate ligament transection (ACLT) surgery to establish an OA model. The ACLT procedure is a well-established method for inducing OA in rodents, as it leads to the destabilization of the knee joint and the development of degenerative changes characteristic of human OA. After 8 weeks of modeling, Group A rats received an equivalent volume of normal saline by gastric lavage, Group B rats were administered 13 mL/kg of Gu Bi Tang, and Group C rats received 19.5 mg/kg of Amfenac solution by gastric lavage. The dosages of Gu Bi Tang and Amfenac were selected based on previous studies examining the therapeutic effects of these interventions in rodent OA models. The gastric lavage frequency for all three groups was maintained at twice daily. The researchers analyzed cartilage morphological changes using toluidine blue staining, chondrocyte proliferation and apoptosis using the TUNEL method, and the expression of PI3K/AKT/mTOR proteins in chondrocytes using Western blotting. Additionally, the expression of inflammatory factors (TNF-α and IL-1β) in serum was measured using ELISA. Results Staining: Compared to the model group (Group A), both the Gu Bi Tang group (Group B) and the Amfenac group (Group C) showed significant improvement in cartilage tissue, with deeper toluidine blue staining. Toluidine blue staining is a marker of cartilage integrity and glycosaminoglycan content, indicating improved cartilage structure and composition in the treatment groups. Chondrocyte proliferation and apoptosis: Compared to the model group (Group A), both the Gu Bi Tang group (Group B) and the Amfenac group (Group C) significantly reduced chondrocyte apoptosis (P < .05). This reduction in chondrocyte death contributes to a healthier cartilage environment and helps prevent further cartilage degradation. Protein expression: In comparison to the model group (Group A), the expression of PI3K, AKT, and mTOR proteins in the joint cartilage of the Gu Bi Tang group (Group B) and the Amfenac group (Group C) significantly decreased, with the Amfenac group showing a greater reduction than the Gu Bi Tang group (P < .05). The inhibition of this detrimental PI3K/AKT/mTOR signaling pathway promotes chondrocyte survival and a more favorable cartilage homeostasis. Inflammatory factor expression: Prior to treatment, there was no significant difference in the expression levels of the inflammatory factors TNF-α and IL-1β in serum among the three groups (P > .05). However, after treatment, both the Gu Bi Tang group (Group B) and the Amfenac group (Group C) showed a significant reduction in the serum expression of TNF-α and IL-1β compared to the model group (Group A), with the Amfenac group showing a greater reduction than the Gu Bi Tang group (P < .05). This is important, as TNF-α and IL-1β are key pro-inflammatory cytokines that drive the destructive processes in osteoarthritis. Conclusion In summary, this study demonstrates that Gu Bi Tang exerts protective effects on chondrocytes in a rat model of osteoarthritis. Specifically, Gu Bi Tang was shown to inhibit chondrocyte apoptosis, reduce the expression of key proteins in the PI3K/AKT/mTOR signaling pathway, and decrease the levels of the pro-inflammatory cytokines TNF-α and IL-1β. These findings suggest that Gu Bi Tang could offer a novel therapeutic approach for osteoarthritis by modulating key signaling pathways and inflammatory responses. The ability of Gu Bi Tang to preserve chondrocyte viability and maintain a more favorable cartilage homeostasis makes it a promising candidate for further investigation as a potential treatment for osteoarthritis. Future studies should explore the precise mechanisms by which Gu Bi Tang exerts its beneficial effects and evaluate its efficacy in additional animal models and clinical settings.
研究领域:
药理学
·
风湿病学
·
骨科
·
分子生物学
·
炎症
✓ 已验证
DOI
PubMed
高影响因子
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