JOURNAL OF NANOPARTICLE RESEARCH
·
2021
·Vol. 23
·期 7
·1-14
·
IF 2.253
Yu Linkang,Lin Runlian,Han Yu,Fan Dehui,Zhou Guoqiang,Zhang Jinchao,Jia Guang,Ge Kun
With the wide use of rare earth nanomaterials in industry, environmental control, and medicine with their unique properties, it has focused on the exposure of humans to the rare earth nanoparticles in recent years. Because of the similar properties of rare earth and calcium, rare earth nanoparticles can deposit in the bone and affect the osteogenic differentiation of bone mesenchymal stem cells (BMSCs). La(OH) 3 nanoparticles are widely used in the catalysis, sensor, electrode, and luminescent materials. However, there are few reports about the bioactivity of La(OH) 3 nanoparticles on the bone metabolism. In this work, three La(OH) 3 nanorods have been got by hydrothermal method, Long-, Medium-, and Short-La(OH) 3 nanorods, the lengths of which were of ~ 640, 255, and 80 nm, and the diameters of which were of ~ 85, 40, and 35 nm, respectively. All the La(OH) 3 nanorods showed no effect on BMSCs viability and the blood compatibility. But the osteogenic differentiation showed a significant difference in La(OH) 3 nanorods, in which Short-La(OH) 3 nanorods showed the highest promoting effect on osteogenic differentiation. The potential mechanism in the osteogenic differentiation caused by three La(OH) 3 nanorods was correlated with the different uptake efficiency in BMSCs and degradation in lysosome to form LaPO 4 . This work on La(OH) 3 nanorods provides the basic data for the development of lanthanum-based nanoparticles. Graphical abstract
研究领域:
纳米技术
·
生物材料
·
干细胞研究
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
Stem Cell Reports
·
2026
·
IF 5.6
Zhe Yang,Xin Li,Niujian Wu,Ling Wang,Zhanjin Lu,Lingling Wang,Shisong Han,Hongyun Lu
Bone marrow mesenchymal stem cell (BMSC) lineage commitment contributes to metabolic bone diseases, but whether glucagon-like peptide-1 (GLP-1) regulates osteo-adipogenic fate remains unclear. Here, RNA sequencing was performed to identify potential pathways regulated by GLP-1 in BMSCs, followed by gain- and loss-of-function experiments. Furthermore, BMSC-specific Hif-2α knockout mice with glucocorticoid-induced osteoporosis were treated with semaglutide to evaluate skeletal effects. GLP-1 suppressed adipogenesis and promoted osteogenesis of BMSCs in a dose-dependent manner. Transcriptomic analysis identified PI3K-AKT and hypoxia signaling as major GLP-1-regulated pathways. Mechanistically, GLP-1 inhibited AKT activation during adipogenesis and reshaped AKT signaling dynamics during osteogenesis. Loss of HIF-2α largely abolished GLP-1-mediated regulation of AKT activity. In vivo , semaglutide improved trabecular bone mass in osteoporotic mice, whereas this bone-protective effect was markedly diminished in Hif-2α -knockout mice. Our findings suggest that GLP-1 modulates BMSC lineage commitment by inhibiting adipogenesis and enhancing osteogenesis through HIF-2α-associated regulation of AKT signaling.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Chenying Zeng,Linjian Chen,Jiajie Lin,Zipeng Xiao,Qingqiang Tu,Wenhui Yu,Weihao Zhang,Qibo Li,Yanfeng Wu,Zhongyu Xie,Ziji Zhang
Background The shift in BMSC differentiation potential toward adipogenesis at the expense of osteogenesis is a critical mechanism underlying reduced bone formation in osteoporosis. Necroptosis has been implicated as a key driver of bone-fat imbalance in osteoporosis, though its mechanisms remain unclear. Taraxasterol (TAX), a bioactive triterpenoid derived from Taraxacum officinale , exhibits antitumor, antioxidant, and immunomodulatory properties. However, its potential role in osteoporosis has not yet been explored. Objective This study aimed to investigate whether TAX alleviates osteoporosis by regulating necroptosis and osteogenic–adipogenic differentiation in BMSCs, and to elucidate the underlying molecular mechanisms. Methods An ovariectomized (OVX) mouse model of osteoporosis was established for in vivo evaluation. Treatment groups received daily oral administration of TAX (5 or 20 mg/kg), with estradiol (E₂, 10 μg/kg) serving as a positive control. Bone microarchitecture and therapeutic response were assessed via micro-CT and immunohistochemistry, while femoral necroptosis and differentiation markers were evaluated by immunostaining. For in vitro studies, BMSCs isolated from osteoporosis patients were treated with the necroptosis inducer TSZ (TNF-α, SM-164, Z-VAD-FMK), with or without TAX. Flow cytometry was used to analyze the phenotype of MSCs. To identify molecular targets and mechanisms, an integrated approach combining network pharmacology, RNA sequencing, SPR assays, and molecular docking was employed. Subsequent analyses included western blotting, PI staining, and RNA interference to assess TAX-regulated necroptosis and PI3K/AKT/PPARγ pathway activity. ARS and ORO staining were employed to analyze osteogenic and adipogenic differentiation, respectively, and mitochondrial function was evaluated with TMRE and MitoSOX Red probes. Results TAX (20 mg/kg) significantly ameliorated bone loss in OVX mice, suppressed femoral necroptotic signaling, and reversed osteogenic–adipogenic imbalance in OVX-derived BMSCs. In vitro , TAX pretreatment attenuated TSZ-induced differentiation imbalance and necroptosis in patient-derived BMSCs and mitigated mitochondrial damage. Integrated network pharmacology and RNA sequencing revealed that TAX targets the PI3K/AKT/PPARγ axis. Immunohistochemical analysis demonstrated upregulation of the PI3K/AKT/PPARγ axis in the femurs of OVX mice following TAX administration. Molecular docking and SPR assays confirmed effective binding between TAX and PI3K. The protective effects of TAX were abolished by the PI3K inhibitor LY294002. Furthermore, TAX enhanced the rebalancing of osteogenic–adipogenic differentiation in PPARγ-silenced BMSCs. Conclusion Our study reveals for the first time that TAX restores osteogenic-adipogenic equilibrium in OP-BMSCs and promotes bone regeneration through PI3K/AKT/PPARγ activation and mitochondrial protection-mediated suppression of necroptosis. These results position TAX as a promising therapeutic candidate for osteoporosis.
研究领域:
药理学
·
分子生物学
·
内分泌学
·
干细胞研究
·
骨代谢
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanotechnology Reviews
·
2020
·Vol. 9
·期 1
·670-682
·
IF 3.639
Min Liu,Lei Wang,Xiaowen Tong,Jiamu Dai,Guang Li,Peihua Zhang,Huaifang Li
To solve the bio-inertness of widely used polypropylene (PP) mesh for treating pelvic floor dysfunction (PFD), a novel strategy of incorporation with elastin gene-transfected bone marrow stem cells (BMSCs) and antibacteria drug-loaded polylactic acid (PLA) nanofibrous mat covering layer was proposed to overcome the limitation of the pristine PP mesh. Then, a series of physicochemical and in vitro experiments were applied to investigate the improvement of the as-prepared material. The elastin protein expression was proved to be upregulated without obvious cytotoxicity influence after the gene transfection and also improved the cell migration rate. In addition, the antibacteria drug-loaded PLA nanofibrous mat on the PP mesh could efficiently inhibit bacteria and showed no significant impact on cell adhesion and proliferation. Thus, we believe that the incorporation of the elastin gene-transfected BMSCs and nanofiber-coated PP mesh would be a potential candidate in the application of female PFD.
研究领域:
生物医学工程
·
组织工程
·
材料科学
·
再生医学
✓ 已验证
产品关联
DOI
高影响因子
Regenerative Biomaterials
·
2021
·Vol. 8
·期 5
·
IF 6.353
Wei Bangguo,Wang Wenrui,Liu Xiangyu,Xu Chenxi,Wang Yanan,Wang Ziqi,Xu Jinnuo,Guan Jianzhong,Zhou Pinghui,Mao Yingji
Critical-sized bone defects caused by traumatic fractures, tumour resection and congenital malformation are unlikely to heal spontaneously. Bone tissue engineering is a promising strategy aimed at developing in vitro replacements for bone transplantation and overcoming the limitations of natural bone grafts. In this study, we developed an innovative bone engineering scaffold based on gelatin methacrylate (GelMA) hydrogel, obtained via a two-step procedure: first, solid lipid nanoparticles (SLNs) were loaded with resveratrol (Res), a drug that can promote osteogenic differentiation and bone formation; these particles were then encapsulated at different concentrations (0.01%, 0.02%, 0.04% and 0.08%) in GelMA to obtain the final Res-SLNs/GelMA scaffolds. The effects of these scaffolds on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and bone regeneration in rat cranial defects were evaluated using various characterization assays. Our in vitro and in vivo investigations demonstrated that the different Res-SLNs/GelMA scaffolds improved the osteogenic differentiation of BMSCs, with the ideally slow and steady release of Res; the optimal scaffold was 0.02 Res-SLNs/GelMA. Therefore, the 0.02 Res-SLNs/GelMA hydrogel is an appropriate release system for Res with good biocompatibility, osteoconduction and osteoinduction, thereby showing potential for application in bone tissue engineering.
研究领域:
组织工程
·
生物材料
·
骨再生
·
干细胞研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2023
·
IF 7
Dan Wei,Mingze Zeng,Borui Su,Yusheng Zhang,Kai Wu,Ting Zhou,Chengheng Wu,Jing Sun,Hongsong Fan
As one of the physical stimulus tools to target neuromodulation-related biological entities, mild thermal stimulus has attracted increasing attention in unraveling neural differentiation processing. However, thermal stimulus for neural behavior regulation has been relatively unexplored due to the challenge in finding a good method of exerting thermal stimulus. Considering the distance-dependent temperature preservation efficiency and the native importance of a bioactive matrix, we herein put forward the design of a photothermal hydrogel by immobilizing photothermal dopamine (DA) in hyaluronic acid (HA) chains. Benefitting from the minuscule disaccharide repeat unit size (≈1 nm) of HA used for the DA grafting, and the additional adhesion capacity of the DA for recruiting cells, a uniformly close distance from heating source to cells is realized. Therefore, we successfully established a near-infrared light initiated photothermal stimulus platform, with full bioactivity and high thermal manipulation efficiency. After extensive characterization, we proved that the thermal activation, from matrix to cells, triggered TRPV1 ion channel opening and Ca2+ influx, which finally promoted neural differentiation of bone marrow mesenchymal stem cells (BMSCs). This work broadens the possibilities of polymeric photothermal materials, and is of great significance for remotely manipulating neural and other cellular machinery for stem cell therapeutics in tissue engineering.
研究领域:
组织工程
·
干细胞生物学
·
神经科学
·
生物医学工程
·
光热治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2020
·
IF 8.724
Wei Zhang,Chen Ling,Aini Zhang,Haoyang Liu,Yujie Jiang,Xiaolong Li,Renwang Sheng,Qingqiang Yao,Jialin Chen
Endogenous repair of osteochondral defect is usually limited by the insufficient number of cells in the early stage and incomplete cell differentiation in the later stage. The development of drug delivery systems for sequential release of pro-migratory and pro-chondrogenic molecules to induce endogenous bone marrow-derived mesenchymal stem cells (BMSCs) recruitment and chondrogenic differentiation is highly desirable for in situ osteochondral regeneration. In this study, a novel, all-silk-derived sequential delivery system was fabricated by incorporating the tunable drug-loaded silk fibroin (SF) nanospheres into a SF porous matrix. The loading efficiency and release kinetics of biomolecules depended on the initial SF/polyvinyl alcohol (PVA) concentrations (0.2%, 1% and 5%) of the nanospheres, as well as the hydrophobicity of the loaded molecules, resulting in controllable and programmed delivery profiles. Our findings indicated that the 5% nanosphere-incorporated matrix showed a rapid release of E7 peptide during the first 120 h, whereas the 0.2% nanosphere-incorporated matrix provided a slow and sustained release of Kartogenin (KGN) longer than 30 days. During in vitro culture of BMSCs, this functional SF matrix incorporated with E7/KGN nanospheres showed good biocompatibility, as well as enhanced BMSCs migration and chondrogenic differentiation through the release of E7 and KGN . Furthermore, when implanted into rabbit osteochondral defect, the SF nanosphere matrix with sequential E7/KGN release promoted the regeneration of both cartilage and subchondral bone. This work not only provided a novel all-silk-derived drug delivery system for sequential release of molecules, but also a functional tissue-engineered scaffold for osteochondral regeneration.
研究领域:
生物材料
·
组织工程
·
药物递送系统
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2025
·
IF 4.8
Mingliang He,Yi Pan,Jiayi Li,Yaqin Qi,Kangbei Zhu,Fangjie Zhang
Purpose This study aimed to address the limitations of synthetic meshes in incisional hernia repair by developing a bioactive composite mesh combining poly(lactic-co-glycolic acid) (PLGA), type I collagen, and bone marrow mesenchymal stem cells (BMSCs). Methods The PLGA scaffolds, fabricated via freeze-drying, were modified with collagen to enhance biocompatibility and loaded with BMSCs to promote tissue regeneration. In vitro and in vivo evaluations in a rat ventral hernia model assessed biomechanical properties, anti-adhesion efficacy, and tissue integration. Results The PLGA-Collagen I-BMSCs mesh exhibited superior anti-adhesion performance, reduced inflammatory cell infiltration by 73.3%, and enhanced neovascularization compared to commercial meshes (Sepramesh™ and Parietex™). BMSCs modulated TGF-β1/Smad3 signaling to mitigate fibrosis, while collagen alignment improved mechanical recovery. The composite mesh degraded at a rate matching tissue regeneration, with 10% PLGA maintaining structural integrity for 20 weeks. Histological analysis revealed organized collagen deposition and minimal adhesions (Nair grade 0–1 in 100% of cases). Conclusion These findings highlight the potential of the PLGA-Collagen I-BMSCs composite as an innovative intraperitoneal onlay mesh (IPOM) solution, offering mechanical stability, anti-adhesive properties, and regenerative bioactivity. This strategy shifts hernia repair from passive support to active tissue regeneration, providing a foundation for next-generation hernia repair materials.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2020
·Vol. 8
·期 8
·2212-2226
·
IF 6.183
Xue Feng,Tong Zhou,Peifang Xu,Juan Ye,Zhongru Gou,Changyou Gao
Due to the poor self-repair capabilities of articular cartilage, chondral or osteochondral injuries are difficult to be recovered. In this study, an N-cadherin mimetic peptide sequence HAVDIGGGC (HAV) was conjugated to direct cell–cell interactions, and an aggrecanase-1 cleavable peptide sequence CRDTEGE-ARGSVIDRC (ACpep) was used to crosslink hyperbranched PEG-based multi-acrylate polymer (HBPEG) with cysteamine-modified chondroitin sulfate (Cys-CS), obtaining an aggrecanase-1 responsively degradable and HAV-conjugated hydrogel ((HAV-HBPEG)-CS-ACpep). A HBPEG-CS-ACpep hydrogel without the HAV motif was also prepared. The two hydrogels exhibited similar equilibrium swelling ratios, elastic moduli and pore sizes after lyophilization, indicating the negligible influence of conjugated HAV on the crosslinking networks and mechanical properties of the hydrogels. After being degraded in PBS, aggrecanase-1 (ADAMTS4) and trypsin, the HBPEG-CS-ACpep hydrogel exhibited significantly decreased elastic moduli with a much lower value when incubated in enzyme solutions. The two hydrogels could maintain the viability of encapsulated bone marrow-derived mesenchymal stem cells (BMSCs), and the (HAV-HBPEG)-CS-ACpep hydrogel better promoted the cell–cell interactions. After being implanted into osteochondral defects in rabbits for 18 weeks, the two cell-laden hydrogel groups achieved better repair effects than the blank control group. Moreover, hyaline cartilage was formed in the (HAV-HBPEG)-CS-ACpep/BMSCs hydrogel group, while a hybrid of hyaline cartilage and fibrocartilage was found in the HBPEG-CS-ACpep/BMSCs hydrogel group.
研究领域:
组织工程
·
再生医学
·
生物材料
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2023
·
IF 6.1
Bing-hao Lin,Run-xun Ma,Jing-tao Wu,Shi-qi Du,Yi-yun Lv,Hao-nan Yu,Wei Zhang,Shu-ming Mao,Guang-yao Liu,Yi-tian Bu,Zi-hao Chen,Chen Jin,Zong-yi Wu,Lei Yang
Osteoporosis (OP) is typically brought on by disruption of bone homeostasis. Excessive oxidative stress and mitochondrial dysfunction are believed to be the primary mechanisms underlying this disorder. Therefore, in order to restore bone homeostasis effectively, targeted treatment of oxidative stress and mitochondrial dysfunction is necessary. Cinnamaldehyde (CIN), a small molecule that acts as an agonist for the nuclear factor erythroid 2-related factor (Nrf2), has been found to possess antiapoptotic, anti-inflammatory, and antioxidant properties. We found that CIN, while rescuing apoptosis, can also reduce the accumulation of reactive oxygen species (ROS) to improve mitochondrial dysfunction and thus restore the osteogenic differentiation potential of BMSCs disrupted by hydrogen peroxide (H2O2) exposure. The role of CIN was preliminarily considered to be a consequence of Nrf2/HO-1 axis activation. The ovariectomized mice model further demonstrated that CIN treatment ameliorated oxidative stress in vivo, partially reversing OVX-induced bone loss. This improvement was seen in the trabecular microarchitecture and bone biochemical indices. However, when ML385 was concurrently injected with CIN, the positive effects of CIN were largely blocked. In conclusion, this study sheds light on the intrinsic mechanisms by which CIN regulates BMSCs and highlights the potential therapeutic applications of these findings in the treatment of osteoporosis.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2019
·
IF 10.273
Chuanchuan Lin,Bailong Tao,Yiman Deng,Ye He,Xinkun Shen,Rong Wang,Lu Lu,Zhihong Peng,Zengzilu Xia,Kaiyong Cai
Bone marrow derived mesenchymal stromal cells (BMSCs) migration to injury site is a prevalent event in tissue repair process after damage occurrence. The migration process is always accompanied with matrix stiffness change. In this study, sodium alginate hydrogels with different stiffness and Transwell chambers with gradient chemical factors were employed to mimic tissue repair in vivo . In this work, in the stiffness range of 1–20 kPa, BMSCs in stiffer matrix showed higher migration speed compared to those in softer matrix. Moreover, stiffer matrix decreased the nuclear stiffness of BMSCs and reduced the expression of lamin A/C, which playing a main role in the regulation of nuclear stiffness. Furthermore, it was found that BMSCs fitted environment by selecting migration strategy. This study provides a novel platform for the investigation of BMSCs migration to mimic the natural tissue repair process.
研究领域:
细胞生物学
·
组织工程
·
生物力学
✓ 已验证
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2024
·
IF 6.9
Weicheng Qin,Qi Shang,Gengyang Shen,Bing Li,Peng Zhang,Yuzhuo Zhang,Wenhua Zhao,Honglin Chen,Huiwen Liu,Bin Xie,Zhida Zhang,Hui Ren,Xiaobing Jiang
Diabetes can lead to a disorder of bone-fat balance, a significant cause of osteoporosis due to changes in environmental factors. Baicalin (Bai), an active ingredient of Scutellaria baicalensis , has been confirmed to possess antioxidant, hypoglycemic, and anti-osteoporotic effects. However, a comprehensive understanding of Bai's influence on diabetic osteoporosis (DOP), including its effects and underlying mechanisms, remains elusive. This study investigated Bai's impact on the bone-fat equilibrium in rats with DOP. The results indicated that Bai alleviated bone damage in DOP by promoting osteogenesis and inhibiting adipogenesis. Concurrently, through bioinformatics analysis, it was suggested that Bai's mechanism of action might involve the P38-MAPK pathway. In vitro , Bai was found to enhance the development of bone marrow mesenchymal stem cells (BMSCs) towards osteogenic lineages while suppressing their differentiation towards adipogenic lineages. It was discovered that Bai's promotion of BMSC osteogenic differentiation depends on the P38-MAPK pathway. Additionally, the synergistic effect mediated by Bai and P38-MAPK inhibitor suppressed BMSC adipogenic differentiation. Our research indicates that the P38-MAPK pathway play a role in Bai's effects on the osteogenic-adipogenic differentiation of BMSCs, showcasing the potential for DOP treatment. This study highlights Bai's ability to regulate the equilibrium between bone and fat, presenting a novel approach to adressing DOP.
研究领域:
药理学
·
内分泌学
·
骨科学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）