MEDIATORS OF INFLAMMATION
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2017
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IF 3.232
Tao Cheng,Yaochao Zhao,Bin Li,Mengqi Cheng,Jiaxing Wang,Xianlong Zhang
Wear particle-induced chronic inflammation and osteoclastogenesis are two critical factors in the osteolytic process. Curcumin (CUR) is an active compound of the medicinal herb Curcuma longa and has anti-inflammatory and antiosteoclastogenic properties. Our study tested the hypothesis that CUR might attenuate polymethylmethacrylate- (PMMA-) induced inflammatory osteolysis using mouse calvaria osteolysis model in vivo and in vitro. The mice were divided into four groups: phosphate-buffered saline group, CUR, PMMA, and PMMA + CUR groups. Three days before PMMA particle implantation, the mice were intraperitoneally injected with CUR (25 mg/kg/day). Ten days after the operation, the mouse calvaria was harvested for microcomputed tomography, histomorphometry, and molecular biology analysis. As expected, CUR markedly reduced the secretion of tumor necrosis factor-α, interleukin- (IL-) 1β, and IL-6 in the calvarial organ culture. Moreover, CUR suppressed osteoclastogenesis and decreased bone resorption in vivo compared with PMMA-stimulated calvaria. Furthermore, CUR downregulated the osteoclast-specific gene expression and reversed the receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin messenger RNA and protein ratio in PMMA particle-stimulated mice. These results suggest that CUR attenuated PMMA particle-induced inflammatory osteolysis by suppressing the RANKL signaling pathway in the murine calvarium, which could be a candidate compound to prevent and treat AL.
研究领域:
药理学
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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
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2020
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IF 2.985
Yafei Wang,Huimin Liu,Jianmin Wu,Yunjian Liao,Daifeng Lu,Feng Dong,Hongxi Li,Zhitao Zhang,Yongyun Lian
Periprosthetic osteolysis (PIO) caused by wear particles is the main cause of implant failure, which is regulated by nuclear factor κ B receptor activator ligand (RANKL)/osteoprotegerin (OPG) system. At present, there is a lack of effective drugs to prevent or treat PIO. Previous studies have confirmed that DNA methylation is closely related to postmenopausal osteoporosis and can affect the expression of OPG and RANKL . However, the relationship between DNA methylation and PIO is not clear. In this study, we investigated the inhibitory effect of 5-Aza-2-deoxycytidine (AzadC) on osteolysis induced by titanium particles in a mouse model. This inhibition mechanism is achieved by changing the ratio of RANKL/OPG in the osteolysis model. In conclusion, there is a relationship between DNA methylation and PIO. AzadC has a certain inhibitory effect on osteolysis induced by titanium particles. Regulating DNA methylation may be a new way to treat PIO. Our findings lay a foundation for epigenetic understanding and intervention of osteolysis.
研究领域:
骨科
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表观遗传学
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生物材料科学
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产品关联
DOI
PubMed
高影响因子
Materials Today Bio
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2025
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IF 10.2
Hanrui Xi,Xihao Jiang,Shilang Xiong,Yinuo Zhang,Jingyu Zhou,Min Liu,Zhigang Zhou,Chengyu Zhang,Shiwei Liu,Zhisheng Long,Jianguo Zhou,Guowen Qian,Long Xiong
Exacerbation of osteolysis in osteoporotic bone defects presents a significant challenge for implant-based treatments. This underscores the urgent need to develop implants that actively mitigate osteolysis while simultaneously promoting bone regeneration. In this study, the osteogenic potential of mesoporous bioactive glass (MBG) and β-tricalcium phosphate (β-TCP) was combined with the anti-bone resorption property of Ga doping. Ga-MBG was synthesized using a self-transformation method and subsequently incorporated into β-TCP at concentrations of 5 wt%, 10 wt% and 15 wt%. Scaffolds were prepared using extrusion-based 3D printing. The cytocompatibility of the composite scaffolds and their regulatory effects on the differentiation of osteoblasts and osteoclasts were systematically examined. In addition, the molecular mechanisms underlying bone regeneration and osteolysis regulation in osteoblasts were explored. Subsequently, cranial defects were repaired in a rat model of osteoporosis to assess the therapeutic efficacy and biological safety of the optimal concentration of the Ga-MBG/TCP composite scaffold. These findings indicated that the 10 wt% Ga-MBG/TCP composite scaffold exhibited excellent biocompatibility, enhanced new bone formation, and effectively mitigated osteolysis. These results provide a foundation for further investigation into the optimal concentration of Ga-MBG implants and highlight their potential application in future therapies for osteoporotic bone defects.
研究领域:
生物材料学
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骨科医学
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再生医学
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产品关联
DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
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2024
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IF 4.7
Long Zhang,Weibin Li,Xiaohui Chen,Dongmin Cao,Siyuan You,Fan Shi,Zhengqiong Luo,Hongyu Li,Xiangchen Zeng,Yabin Song,Na Li,Yoshie Akimoto,Gang Rui,Yu Chen,Zuoxing Wu,Ren Xu
Bone metastases caused by breast cancer pose a major challenge to the successful treatment of breast cancer patients. Many researchers have suggested that herbal medicines are extremely effective at preventing and treating cancer-associated osteolysis. Previous studies have revealed that Morusin (MOR) is cytotoxic to many cancer cells ex vivo . Nevertheless, how MOR contributes to osteolysis induced by breast cancer is still unknown, and the potential mechanism of action against osteolysis is worthy of further study. The protective effect and molecular mechanism of MOR in inhibiting breast cancer cell-induced osteolysis were verified by experiments and network pharmacology. Cell function was assessed by cell proliferation, osteoclast (OC) formation, bone resorption, and phalloidin staining. Tumour growth was examined by micro-CT scanning in vivo . To identify potential MOR treatments, the active ingredient–target pathway of breast cancer was screened using network pharmacology and molecular docking approaches. This study is the first to report that MOR can prevent osteolysis induced by breast cancer cells. Specifically, our results revealed that MOR inhibits RANKL-induced osteoclastogenesis and restrains the proliferation, invasion and migration of MDA-MB-231 breast cells through restraining the PI3K/AKT/MTOR signalling pathway. Notably, MOR prevented bone loss caused by breast cancer cell-induced osteolysis in vivo , indicating that MOR inhibited the development of OCs and the resorption of bone, which are essential for cancer cell-associated bone distraction. This study showed that MOR treatment inhibited osteolysis induced by breast cancer in vivo . MOR inhibited OC differentiation and bone resorption ex vivo and in vivo and might be a potential drug candidate for treating breast cancer-induced osteolysis.
研究领域:
肿瘤学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2022
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IF 5.988
Zuoxing Wu,Chen Li,Yu Chen,Qian Liu,Na Li,Xuemei He,Weibin Li,Rong Shen,Li Li,Chenming Wei,Siyuan Shao,Fangsheng Fu,Jiaxin Ding,Xiaochen Sun,Dairong Wang,Guixin Yuan,Yiji Su,Jinmin Zhao,Jiake Xu,Ren Xu,Xin Xu,Feng Xu
Bone homeostasis only exists when the physical function of osteoblast and osteoclast stays in the balance between bone formation and resorption. Bone resorption occurs when the two processes are uncoupled, shifting the balance in favour of bone resorption. Excessive activation of osteoclasts leads to a range of osteolytic bone diseases including osteoporosis, aseptic prosthesis loosening, rheumatoid arthritis, and osteoarthritis. Receptor activator of nuclear factor kappa-B ligand (RANKL) and its downstream signaling pathways are recognized as key mediators that drive the formation and activation of osteoclastic function. Hence, osteoclast formation and/or its function remain as dominant targets for research and development of agents reaching the treatment towards osteolytic diseases. Chrysin (CHR) is a flavonoid with a wide range of anti-inflammatory and anti-tumor effects. However, its effect on osteoclasts remains unknown. In this study, we found the effects of CHR on inhibiting osteoclast differentiation which were assessed in terms of the number and size of TRAcP positive multinucleated osteoclasts (OCs). Further, the inhibitory effects of CHR on bone resorption and osteoclast fusion of pre-OC were assessed by hydroxyapatite resorption pit assay and F-actin belts staining; respectively. Western blotting analysis of RANKL-induced signaling pathways and immunofluorescence analysis for p65 nuclear translocation in response to RANKL-induced osteoclasts were used to analyze the mechanism of action of CHR affecting osteoclasts. Lastly, the murine calvarial osteolysis model revealed that CHR could protect against particle-induced bone destruction in vivo . Collectively, our data strongly suggested that CHR with its promising anti-tumor effects would also be a potential therapeutic agent for osteolytic diseases.
研究领域:
药理学
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骨科
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2023
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IF 9.5
Huajun Pan,Xinxin Miao,Jianjian Deng,Chongzhi Pan,Xigao Cheng,Xiaolei Wang
The disability rate of joint diseases can be reduced by the use of artificial joints, but joint loosening at a late state limits the lifespan and surgical efficacy of the joints. Wear particles can be recognized by macrophages and induce cells to produce reactive oxygen species (ROS) and inflammatory factors, causing persistent inflammation and decreased osteogenic activity, which ultimately leads to loosening of joint prostheses. Here, the platinum (Pt) nanozymes with excellent ROS scavenging and anti-inflammatory capabilities were encapsulated in zinc imidazolium zeolite framework-8 (ZIF-8), and then the osteogenic active element lanthanum (La) was introduced through ion exchange to finally construct a bimetallic metal–organic framework (Pt@ZIF-8@La). In vitro and in vivo experiments demonstrated that this multifunctional nanoplatform possessed the functions of efficient scavenging of ROS, immune regulation, and promotion of osteogenic differentiation. Meanwhile, the mechanism is explored that Pt@ZIF-8@La can also promote osteogenic mineralization by upregulating the ratio of the osteoprotegerin (OPG)/receptor activator of the NF-κB ligand (RANKL), which can achieve a synergistic therapeutic effect of immunomodulation and osteogenesis, thereby realizing the purpose of relieving aseptic osteolysis.
研究领域:
材料科学
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生物医学工程
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骨科
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纳米技术
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产品关联
DOI
PubMed
高影响因子
Biomolecules
·
2021
·Vol. 11
·期 3
·480
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IF 4.879
Yujie Han,Weihao Shao,Dan Zhong,Cui Ma,Xiaona Wei,Abrar Ahmed,Tingting Yu,Wei Jing,Lili Jing
Multicentric carpotarsal osteolysis (MCTO) is a rare skeletal dysplasia with osteolysis at the carpal and tarsal bones. Heterozygous missense mutations in the transcription factor MAFB are found in patients with MCTO. MAFB is reported to negatively regulate osteoclastogenesis in vitro. However, the in vivo function of MAFB and its relation to MCTO remains unknown. In this study, we generated zebrafish MAFB homologmafbbmutant utilizing CRISPR/Cas9 technology.Mafbbdeficient zebrafish demonstrated enhanced osteoclast cell differentiation and abnormal cartilage and bone development resembling MCTO patients. It is known that osteoclasts are hematopoietic cells derived from macrophages. Loss ofmafbbcaused selective expansion of definitive macrophages and myeloid cells, supporting thatmafbbrestricts myeloid differentiation in vivo. We also demonstrate that MAFB MCTO mutations failed to rescue the defective osteoclastogenesis inmafbb−/−embryos, but did not affect osteoclast cells in wild type embryos. The mechanism of MCTO mutations is likely haploinsufficiency. Zebrafishmafbbmutant provides a useful model to study the function of MAFB in osteoclastogenesis and the related MCTO disease.Keywords:MAFB;Multicentric Carpotarsal Osteolysis (MCTO);osteoclasts;macrophage and monocytes;zebrafish
研究领域:
遗传学
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发育生物学
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骨骼疾病
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产品关联
DOI
PubMed
高影响因子
Small
·
2022
·Vol. 18
·期 29
·2107787
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IF 15.153
Haifeng Liang,Lei Zhou,Zhichao Hu,Yuxiang Ge,Taiwei Zhang,Qing Chen,Ben Wang,Shunyi Lu,Wang Ding,Jian Dong,Fengfeng Xue,Libo Jiang
Low responsiveness to anti-programmed death-1/programmed death-ligand 1 (anti-PD-1/PD-L1) for solid tumors indicates the presence of other immunosuppressive pathways. Siglec15, a newly discovered immune checkpoint, has been reported to repress immune responses in the tumor microenvironment (TME) and regulate osteoclast differentiation. However, the role of Siglec15 in the treatment for bone metastasis remains unclear. Herein, Siglec15 shows significantly higher expression in lung adenocarcinoma spinal metastasis (LUAD-SM) than in para-cancerous spinal tissues and primary LUAD. Subsequently, a TME-responsive hollow MnO 2 nanoplatform (H-M) loaded with Siglec15 siRNA and cisplatin (H-M@siS15/Cis) is developed, and the surface is modified with an aspartic acid octapeptide (Asp 8 ), thus allowing H-M to target spinal metastasis. High drug-loading capacity, good biocompatibility, effective tumor accumulation, and efficient Siglec15 silencing are demonstrated. Furthermore, the nanoparticles could reverse immunosuppression caused by tumor cells and tumor-associated macrophages (TAMs) and inhibit osteoclast differentiation via Siglec15 downregulation in vitro. In a LUAD-SM mouse model, H-M@siS15/Cis-Asp 8 exhibits superior therapeutic efficacy via synergetic immunochemotherapy and osteolysis inhibition. Taken together, this single nanoplatform reveals the therapeutic potential of the new immune checkpoint Siglec15 in LUAD-SM and provides a strategy to treat this disease.
研究领域:
肿瘤学
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免疫学
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纳米医学
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骨生物学
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产品关联
DOI
PubMed
高影响因子
Bioactive Materials
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2020
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IF 8.724
Yichuan Pang,Li Su,Yao Fu,Fan Jia,Chenxi Zhang,Xiankun Cao,Wenxin He,Xueqian Kong,Jiake Xu,Jie Zhao,An Qin
Breast cancer bone metastasis poses significant challenge for therapeutic strategies. Inside the metastatic environment, osteoclasts and tumor cells interact synergistically to promote cancer progression. In this study, the proprotein convertase furin is targeted due to its critical roles in both tumor cell invasion and osteoclast function. Importantly, the furin inhibitor is specifically delivered by bone targeting superparamagnetic iron oxide (SPIO) nanoparticles. Our in vitro and in vivo data demonstrate that this system can effectively inhibit both osteoclastic bone resorption and breast cancer invastion, leading to alleviated osteolysis. Therefore, the bone targeting & furin inhibition nanoparticle system is a promising therapeutic and diagnostic strategy for breast cancer bone metastasis.
研究领域:
肿瘤学
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纳米技术
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生物材料
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癌症转移
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DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
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2019
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IF 4.511
Ying Yang,Lihong Liu,Hang Luo,Dou Zhang,Shaorong Lei,Kechao Zhou
Currently, implant-related bone infection characterized by aggravated bone resorption and osteolysis, remains a severe challenge in plastic and orthopedic surgery. Therefore, surface modification of implants endowed with both antibacterial potential and suppression of osteoclastogenesis offers new insight into relevant therapeutic strategies. In this study, we designed magnesium (Mg)-incorporated nanotube-modified titanium implants (NT-Mg) that combine dual-functional Mg with antimicrobial properties of titania nanotubes with specific diameter. The surface characterization, in vitro degradation, antibacterial properties, cytocompatibility, and inhibitory effects on osteoclastogenesis together with the in vivo anti-infection potential and osseointegration of the implants were systematically investigated. Our results demonstrated that NT-Mg implants maintained continuous and reliable release of Mg ion from the titania nanotubes (TNTs), producing long lasting antimicrobial activity. The nanotubular structure and alkaline microenvironment during degradation were the two main reasons responsible for the antimicrobial properties of NT-Mg. In addition, NT-Mg exhibited favored osteoprogenitor cell adhesion and proliferation without obvious cytotoxicity. Moreover, Mg2+ released in the degraded liquid suppressed osteoclastogenesis via down-regulation of NF-κB/NFATc1 signaling. Finally, we established an implant-related bone infection model to assess the in vivo anti-infection potential and osseointegration of the NT-Mg implant. As expected, NT-Mg implants significantly prevented bone infection and osteolysis, leading to improved osseointegration. Based on these promising findings, the dual-functional magnesium-incorporated titania nanotubes represent an efficient alternative to realize better osseointegration in severe implant-related bacterial infections.
研究领域:
材料科学
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生物医学工程
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骨科手术
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表面化学
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生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2024
·Vol. 28
·期 7
·e18157
·
IF 4.3
Hui Jiang,Yang Wang,Zhao Tang,Xianjiang Peng,Chan Li,Yangjie Dang,Rui Ma
Periprosthetic osteolysis (PPO) caused by wear particles is one of the leading causes of implant failure after arthroplasty. Macrophage polarization imbalance and subsequent osteogenic inhibition play a crucial role in PPO. Calycosin (CA) is a compound with anti-inflammatory and osteoprotective properties. This study aimed to evaluate the effects of CA on titanium (Ti) particle-induced osteolysis, Ti particle-induced macrophage polarization and subsequent osteogenic deficits, and explore the associated signalling pathways in a Ti particle-stimulated calvarial osteolysis mouse model using micro-CT, ELISA, qRT-PCR, immunofluorescence and western blot techniques. The results showed that CA alleviated inflammation, osteogenic inhibition and osteolysis in the Ti particle-induced calvarial osteolysis mouse model in vivo. In vitro experiments showed that CA suppressed Ti-induced M1 macrophage polarization, promoted M2 macrophage polarization and ultimately enhanced osteogenic differentiation of MC3T3-E1 cells. In addition, CA alleviated osteogenic deficits by regulating macrophage polarization homeostasis via the NF-κB signalling pathway both in vivo and in vitro. All these findings suggest that CA may prove to be an effective therapeutic agent for wear particle-induced osteolysis.
研究领域:
骨科
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药理学
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免疫学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2021
·
IF 13.273
Xinkun Shen,Kendrick Hii Ru Yie,Xinghai Wu,Zixin Zhou,Anba Sun,Abdullrahman M. Al-bishari,Kai Fang,Mohammed A. Al- Baadani,Zhennan Deng,Pingping Ma,Jinsong Liu
Endowed with superior tailorability and functionality, metal–organic frameworks (MOFs) have been exploited for their diverse applications in biomedicine. However, the instability of MOFs under an aqueous environment causes an accelerated degradation preventing their clinical applications and commercialization. To address this issue, studies have reported the incorporation of hydrophobic functional groups into MOF to enhance its stability. In this study, we aimed to fabricate a multifunctional coating on titanium implants by exploiting the synergy between Zn-based MOFs and raloxifene (Ral). We theorized that the integration of MOF and Ral will not only locally deliver the drug, but also take advantage of the hydrophobic functional group of Ral to enhance the stability of MOF in an aqueous environment. The release studies showed a sustained release of both Zn 2+ and Ral for more than 14 d. In-depth in vitro investigations also verified that MOF/Ral coatings significantly enhanced the cell viability and osteogenic differentiation of osteoblasts, as well as decreasing the tartrate-resistant acid phosphatase activity and osteoclastic biomarker expressions. In addition, both micro-computed tomography and immunohistochemical analysis further confirmed the efficacy of MOF/Ral coatings in the formation of new bone within the femurs of osteoporotic rats. The feasibility of MOF/Ral coated titanium implants in inhibiting osteolysis and promoting osteogenesis has undoubtedly proved their clinical prospects in the treatment of osteoporotic bone injury.
研究领域:
生物医学工程
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材料科学
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药学
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骨科
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）