ACS Applied Materials & Interfaces
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2025
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IF 8.2
Haoyang Liu,Yue Zhu,Weixu Chen,Renwang Sheng,Chuanquan Liu,Yuzhi Sun,Jia Liu,Mingyue Wang,Jun Lu,Jialin Chen,Wei Zhang
The advancement of nanomedicine requires a thorough understanding of the intrinsic bioactivity and molecular interactions of nanomaterials for safe and effective clinical applications, which remains lacking for most currently developed nanomaterials. Here, we uncover the unique intrinsic bioactivity and regulatory mechanisms of carbon-based fullerol nanomaterials through high-throughput molecular analysis and explore their therapeutic potential for tissue regeneration using tissue engineering approaches. Fullerol exhibits intrinsic pro-differentiation and antioxidant properties that enhance the osteogenesis and chondrogenesis of MSCs. Mechanistically, proteomic analysis combined with small-molecule inhibition studies reveals that fullerol is internalized by MSCs via clathrin-mediated endocytosis and activates NRF2 signaling, thereby exerting antioxidant effects that restore impaired MSC viability and differentiation under oxidative stress. Leveraging these unique bioactivities, we develop a fullerol-functionalized hydrogel with feasible physicochemical properties and triple biological functions in antioxidant, pro-osteogenic, and pro-chondrogenic effects and confirm its great regenerative capacity for both cartilage and subchondral bone by promoting structural restoration and improving functional recovery in a rat osteochondral defect model. Our findings offer new insights into the intricate interactions between stem cells and nanomaterials at the cellular and molecular levels and broaden the potential biomedical applications of fullerol for future cartilage and bone regeneration therapies.
研究领域:
再生医学
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纳米生物学
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分子生物学
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DOI
PubMed
高影响因子
Food & Function
·
2021
·Vol. 12
·期 14
·6626-6636
·
IF 5.396
Ji Liu,Tianyu Li,Haiyun Chen,Qian Yu,Chunyan Yan
Polygonatum sibiricum Red., a kind of edible and medicinal plant, has a long history of use in traditional Chinese medicine and as a nutritional food additive. Water-soluble crude polysaccharide (PS50) was obtained from P. sibiricum rhizome. After deproteinization and dialysis, PS50 was isolated and purified via DEAE-52 cellulose and Sephadex G-75 gel filtration chromatography to obtain two novel polysaccharides (PSP50-2-1 and PSP50-2-2). Chemical analysis and nuclear magnetic resonance (NMR) studies indicated that PSP50-2-1 was composed of β-D-Glcp-(1→, →2)-β-D-Galp-(1→, →2,6)-β-D-Galp-(1→, β-D-Fruf-(2→, and PSP50-2-2 was composed of β-D-Glcp-(1→, β-D-Galp-(1→, →2)-β-D-Galp-(1→, →6)-β-D-Galp-(1→, →2,6)-β-D-Galp-(1→, β-D-Fruf-(2→. The morphological analysis suggested that PSP50-2-1 and PSP50-2-2 both had a rough surface with cracks. Pharmacological studies showed that PSP50-2-2 at concentrations of 2.59 and 5.19 μM significantly promoted the differentiation and mineralization of MC3T3-E1 cells in vitro, which indicated that PSP50-2-2 had a function of osteogenic activity. Above all, this study provides evidence that PSP50-2-2 may be used as an anti-osteoporotic agent, with applications in health-care and pharmaceutical industries.
研究领域:
药理学
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生物化学
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DOI
PubMed
高影响因子
JOURNAL OF BONE AND MINERAL RESEARCH
·
2025
·
IF 5.9
Liu Qian,Gan Ying,Hu Xingli,Liu Wei,Liao Xiaoxia,Zhang Jingyun,Li Xiaoxia,Zhou Jie,Wang Baoli
Lysine demethylase 6B (KDM6B) plays a role in regulating osteoblast differentiation and fetal bone ossification. Nevertheless, its involvement in regulating postnatal bone homeostasis and bone mass accrual remains unclear. In this study, we generated mice lacking Kdm6b gene specifically in mesenchyme and osteoprogenitor cells using a conditional strategy. The adult mice of both mutant strains had decreased cancellous bone mass. The absence of Kdm6b in mesenchyme led to decreased numbers of osteoblasts and osteoclasts, increased marrow adipocytes, as well as repressed bone formation and resorption. Additionally, Kdm6b-deficient bone marrow stromal cells (BMSCs) displayed impaired osteogenic differentiation and exerted an inhibitory effect on osteoclastogenesis. RNA-seq combined with gene expression analysis uncovered downregulation of collagen triple helix repeat containing 1 (CTHRC1) and a lower receptor activator of nuclear factor κB ligand (RANKL)/osteoprotegerin (OPG) ratio in BMSCs of the mutant mice. Further mechanistic explorations demonstrated that KDM6B epigenetically upregulated CTHRC1 expression by removing the repressive H3K27me3 mark from its promoter, thereby triggering PKCδ/MAPKs signaling to facilitate osteoblast differentiation. CTHRC1 was able to mitigate the dysregulated osteogenic and adipogenic differentiation induced by Kdm6b deficiency. This study provides evidence that KDM6B regulates postnatal bone homeostasis through balancing osteoblast and osteoclast differentiation. Given its predominant promotion of osteoblastic bone formation over osteoclastic bone resorption, KDM6B tends to promote postnatal bone mass accrual.
研究领域:
分子生物学
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骨骼发育
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表观遗传学
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DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2021
·
IF 7.328
Yongmei Ge,Kui Wang,Huili Li,Ye Tian,Yutong Wu,Zhaowei Lin,Yangyang Lin,Yansong Wang,Jiarong Zhang,Bin Tang
Bone pain is the primary problem for patients with osteoporosis. Ketoprofen is clinically used to treat osteoporotic pain, while long-term oral administration of ketoprofen can cause some side effects. In addition, osteoporosis is also accompanied by bone mass loss and inflammation. In this study, we designed a multifunctional drug (Ket@Mg-MOF-74) adopted Mg-MOF-74 to load ketoprofen to treat osteoporotic pain, bone loss and inflammation comprehensively. Mg-MOF-74 was prepared, and the physicochemical characterization proved that it had excellent physical and chemical stability. Ket@Mg-MOF-74 was synthesized by post-synthetic modification method and a high loading rate of ketoprofen was confirmed. Drug release and ion release experiments indicated Ket@Mg-MOF-74 had a good controlled release of ketoprofen and Mg in solution. Cell experiments in vitro proved the compound drug could significantly reduce the expression of pain-related genes of cyclooxygenase 2 (COX2), obviously up-regulated the expression of osteogenic cytokines and remarkably down-regulated the secretion of pro-inflammatory factors. Therefore, Ket@Mg-MOF-74 is believed a promising painkiller for osteoporotic bone pain, with the function of anti-inflammatory and promoting bone formation.
研究领域:
药理学
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材料科学
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骨生物学
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DOI
PubMed
高影响因子
Frontiers in Molecular Biosciences
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2025
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IF 4
Lian Zhu,Liu Xie,Ziming Wang,Kai-Lin Li,Wei Cai
Introduction The bioactive compound 3,5-DiCQA, derived from Duhaldea nervosa, has been traditionally utilized in folk remedies for bone fractures and osteoporosis. However, its therapeutic mechanisms remain unclear. Methods We employed UHPLC-Q Exactive Orbitrap MS-based cell metabolomics to investigate the molecular mechanisms of 3,5-DiCQA in MC3T3-E1 cells. Cell proliferation was assessed via MTT assay, differentiation by alkaline phosphatase (ALP) activity, and mineralization through alizarin red staining and cetylpyridinium chloride quantification. Metabolomic profiling compared drug-treated and control groups. Results Results from MTT assays demonstrated that 3,5-DiCQA significantly promoted cell proliferation at 100 μM. Alkaline phosphatase (ALP) assays and alizarin red staining revealed enhanced osteoblast differentiation and mineralization, respectively. Calcification deposition was significantly increased in the calcified stained cells by cetylpyridinium chloride quantization, indicating that 3,5-DiCQA can promote the mineralization of MC3T3-E1 cells. Metabolomic analysis identified key metabolic changes, including the downregulation of phytosphingosine and upregulation of sphinganine and citric acid. Discussion These findings suggest that 3,5-DiCQA promotes osteoblast proliferation, differentiation and mineralization through pathways such as sphingolipid metabolism, arginine and proline metabolism, mucin type O-glycan biosynthesis and the citrate cycle (TCA cycle). This study provides insights into the therapeutic potential of 3,5-DiCQA for osteoporosis and highlights the utility of metabolomics in elucidating traditional Chinese medicine (TCM).
研究领域:
药理学
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代谢组学
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骨生物学
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DOI
PubMed
高影响因子
RSC Advances
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2020
·Vol. 10
·期 17
·9777-9785
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IF 3.119
Maihemuti Yakufu,Zongliang Wang,Yu Wang,Zixue Jiao,Min Guo,Jianguo Liu,Peibiao Zhang
Polyetheretherketone (PEEK), as the most promising implant material for orthopedics and dental applications, has bone-like stiffness, excellent fatigue resistance, X-ray transparency, and near absence of immune toxicity. However, due to biological inertness, its bone conduction and bone ingrowth performance is limited. The surface modification of PEEK is an option to overcome these shortcomings and retain most of its favorable properties, especially when excellent osseointegration is desired. In this study, a simple reaction procedure was employed to bind the osteogenic growth peptide (OGP) on the surface of PEEK materials by covalent chemical grafting to construct a bioactive interface. The PEEK surface was activated by N,N′-disuccinimidyl carbonate (DSC) after hydroxylation, and then OGP was covalently grafted with amino groups. The functionalized surface of PEEK samples were characterized by X-ray photoelectron spectroscopy (XPS), Fourier-transform infrared spectroscopy (FT-IR), water contact angle measurement and biological evaluation in vitro. OGP-functionalized PEEK surface significantly promoted the attachment, proliferation, alkaline phosphatase (ALP) activity and mineralization of pre-osteoblast cells (MC3T3-E1). The in vivo rat tibia implantation model is adopted and micro-CT analyses demonstrated that the OGP coating significantly promoted new bone formation around the samples. The in vitro and in vivo results reveal that the modification by covalent chemical functionalization with OGP on PEEK surface can augment new bone formation surrounding implants compared to bare PEEK and PEEK implant modified by covalently attached OGP is promising in orthopedic and dental applications.
研究领域:
生物材料学
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骨科医学
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2018
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IF 8.097
Hongyu Quan,Yuwei He,Jujiang Sun,Weihu Yang,Wei Luo,Ce Dou,Fei Kang,Chunrong Zhao,Jian He,Xiaochao Yang,Shiwu Dong,Hong Jiang
Bone defects/fractures are common in older people suffering from osteoporosis. Traditional hydroxyapatite (HA) materials for osteoporotic bone repair face many challenges, including limited bone formation and aseptic loosening of orthopedic implants. In this study, a new multifunctional HA is synthesized by spontaneous assembly of alendronate (AL) and Fe3O4 onto HA nanocrystals for osteoporotic bone regeneration. The chemical coordination of AL and Fe3O4 with HA does not induce lattice deformation, resulting in a functionalized HA (Func-HA) with proper magnetic property and controlled release manner. The Func-HA nanocrystals have been encapsulated in polymer substrates to further investigate their osteogenic capability. In vitro and in vivo evaluations reveal that both AL and Fe3O4, especially the combination of two functional groups on HA, can inhibit osteoclastic activity and promote osteoblast proliferation and differentiation, as well as enhance implant osseointegration and accelerate bone remodeling under osteoporotic condition. The as-developed Func-HA with coordinating antiresorptive ability, magnetic property, and osteoconductivity might be a desirable biomaterial for osteoporotic bone defect/fracture treatment.
研究领域:
生物材料学
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骨科医学
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纳米医学
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DOI
PubMed
高影响因子
CRYSTENGCOMM
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2022
·Vol. 24
·期 8
·1546-1555
·
IF 3.756
Ming Wang,Yunli Wang,Yue Tian,Yingchun Zhu
Sr doping in hydroxyapatite (HA) biomaterials has attracted continuous interest due to its well-known positive effects on bone formation. Investigating the effects of Sr on the HA crystal structure is of primary importance for understanding the underlying mechanisms of structure–property relationship. However, the effect of Sr on the HA crystal structure is still controversial and incomplete. Herein, the anisotropic effects of Sr doping on the HA crystal structure are determined by experimental, theoretical and simulative investigations. The good agreement of the results suggests that Sr preferentially replaces Ca(1) sites in the HA structure with a Sr content of 10 mol%, and causes significantly larger expansion in the c-axis direction than in the a-axis direction. The relative expansion rate in the c-axis direction is about 2.22 times that in the a-axis direction, which induces an increased aspect ratio of Sr-HA nanocrystals. When Sr replaces Ca(1) sites, the Sr–O bond length in the SrO6 configuration increases compared with that in Ca(1)O6, giving rise to the anisotropic lattice expansion due to the different projection lengths in different directions of this configuration. Moreover, reaction process investigations show that Sr is incorporated in HA by multi-step reactions from Sr-DCPD to Sr-DCPA and to Sr-HA. These findings shed new light on the anisotropic effect of Sr ions on the HA crystal structure, and provide a theoretical basis for development of ion-modified HA biomaterials.
研究领域:
材料科学
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生物医学工程
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DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2022
·
IF 8.025
Ying Peng,Fenbo Ma,Liqiu Hu,Yuqing Deng,Wenqi He,Bin Tang
Bone formation and repair represent a clinical challenge. In this work, we designed and synthesized strontium Astragalus polysaccharide (APS-Sr), a novel polysaccharide compound that should have therapeutic effects on both anti-inflammation and promoting bone formation. Using material characterization techniques, including SEM, FITR, XRD, etc., we verified the successful synthesis of this compound. Moreover, we examined the potential of this compound for promoting bone repair and inhibiting inflammatory response by cell proliferation assay, ALP and Alizarin Red staining experiments and RT-qPCR. The biological experiment results showed that APS-Sr can effectively inhibit inflammatory factors, promote osteogenic differentiation and up-regulate the bone growth factors. It is therefore believed that APS-Sr should be a promising polysaccharide compound in bone-related biomedical applications.
研究领域:
生物材料
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生物医学工程
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药学
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产品关联
DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2022
·Vol. 23
·期 3
·1-10
·
IF 2.751
Furong Wang,Fucai Zhang,Feng Zheng
Long non‑coding (lnc)RNA KCNQ1 opposite strand/antisense transcript 1 (Kcnq1ot1) has been shown to regulate multiple biological processes. However, the functional role of Kcnq1ot1 in osteoporosis and the underlying mechanism are still unclear. The present study aimed to investigate the function of lncRNA Kcnq1ot1 in osteogenic differentiation. Alkaline phosphatase (ALP) activity was measured using an ALP assay kit. Western blotting was performed to assess the expression levels of osteogenic differentiation‑associated proteins. Reverse transcription‑quantitative PCR was performed to detect Kcnq1ot1, microRNA (miR)‑98‑5p and T‑box transcription factor 5 (Tbx5) expression levels. The binding of Kcnq1ot1 with miR‑98‑5p and that of miR‑98‑5p with Tbx5 were predicted by starBase and TargetScan databases, respectively, and verified using dual luciferase reporter assays. The mineralization of MC3T3‑E1 cells was observed using an Alizarin red S staining assay. The results revealed that expression of Kcnq1ot1 was increased and that of miR‑98‑5p was decreased during osteogenic differentiation. Additionally, Kcnq1ot1 was shown to target miR‑98‑5p and inhibit its expression. Inhibiting miR‑98‑5p reversed the inhibitory effect of Kcnq1ot1 knockdown on osteogenic differentiation and mineralization of MC3T3‑E1 cells. Furthermore, Kcnq1ot1 regulated Tbx5 expression via miR‑98‑5p. Overexpressing miR‑98‑5p or downregulating Tbx5 expression reversed the promotive effect of Kcnq1ot1 overexpression on osteogenic differentiation and mineralization of MC3T3‑E1 cells. In conclusion, these findings suggested that Kcnq1ot1 may promote bone formation by inhibiting miR‑98‑5p and upregulating Tbx5. Kcnq1ot1, miR‑98‑5p and Tbx5 may therefore serve as promising targets for the treatment of osteoporosis.
研究领域:
分子生物学
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细胞生物学
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骨骼生物学
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遗传学
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产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2025
·
IF 14.1
Donghao Gan,Yi Ran,Hong Pan,Qinnan Yan,Wenjing Zhang,Bo Zhou,Pengzhi Xu,Rongdong Liao,Haipeng Xue,Will Jiang,Tailin He,Qingyun Jia,Lei Qin,Francis Y Lee,Di Chen,Chuanju Liu,Guozhi Xiao
The mechanosensitive Piezo1 channel protein plays a pivotal role in promoting bone formation and repair; however, its underlying molecular mechanism(s) are poorly defined. Here this study shows that Sirt1 positively regulates Piezo1 expression and activity to promote osteogenesis and bone repair in mice. This study finds that Piezo1 is up-regulated in the cartilage callus during bone repair. Deleting Piezo1 in chondrocytes largely impairs endochondral ossification and mechanically induced osteogenesis and delays fracture healing in mice, while Yoda1 activation of Piezo1 exerts opposite effects. Sirt1 overexpression or activation dramatically increases Piezo1 protein expression in a dose-dependent manner. Sirt1 binds to Piezo1 protein and deacetylates and activates Piezo1 and Ca 2+ influx in chondrocytes. Piezo1 loss in chondrocytes abolishes the ability of Sirt1 activator SRT2104 to accelerate bone repair. Resveratrol (RSV), a natural Sirt1 activator, also potently activates Piezo1 and enhances bone repair. A yeast microcapsule-based oral formulation of RSV (YC-RSV) is developed to improve drug bioavailability and therapeutic efficacy, which highly and selectively targets to the inflammatory fracture site. Thus, it demonstrates that Sirt1 is a novel and potent activator of Piezo1 to promote bone formation and repair, supporting the potential clinical application of Sirt1 activators in promoting bone formation and repair.
研究领域:
分子生物学
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骨骼生物学
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再生医学
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信号转导
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药理学
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2024
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IF 12.8
Liang Wu,Tao Xu,Sen Li,Kai Sun,Ziyang Tang,Hui Xu,Yong Qiu,Zhenhua Feng,Zhen Liu,Zezhang Zhu,Xiaodong Qin
The osteogenic microenvironment (OME) significantly influences bone repair; however, reproducing its dynamic activation and repair processes remains challenging. In this study, we designed injectable porous microspheres modified with composite peptides to investigate cascade alterations in OME and their underlying mechanisms. Poly l -lactic acid microfluidic microspheres underwent surface modifications through alkaline hydrolysis treatment, involving heterogeneous grafting of bovine serum albumin nanoparticles with stem cell-homing peptides (BNP@SKP) and BMP-2 mimicking peptides (P24), respectively. These modifications well-organized the actions of initial release and subsequent in situ grafting of peptides. Cellular experiments demonstrated varied degrees of chemotactic recruitment and osteogenic differentiation in mesenchymal stem cells. Further biological analysis revealed that BNP@SKP targeted the Ras/Erk axis and upregulated matrix metalloproteinase (MMP)2 and MMP9 expression, thereby enhancing initial chemotaxis and recruitment. In vivo studies validated the establishment of a dynamically regulated OME centered on the microspheres, resulting in increased stem cell recruitment, sequential activation of the differentiation microenvironment, and facilitation of in situ osteogenesis without ectopic ossification. In conclusion, this study successfully fabricated composite peptide-modified microspheres and systematically explored the mechanisms of bone formation through sequential activation of OME via heterogeneous grafting of signaling molecules. This provides theoretical evidence for biomaterials based on microenvironment regulation.
研究领域:
生物材料学
·
骨组织工程
·
细胞生物学
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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）