JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
·
2021
·Vol. 35
·期 7
·e22778
·
IF 3.652
Delu Zheng,Chenli Cui,Chen Shao,Yanqiu Wang,Chengsong Ye,Gaoyou Lv
Coenzyme Q10 (CoQ10) has been reported to improve bone density and the number of trabeculae in postmenopausal osteoporosis, but the mechanism remains to be elucidated. We aimed to investigate the effects of CoQ10 on receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and the underlying molecular mechanisms. RAW264.7 cells were treated with different concentrations of RANKL to differentiate into osteoclasts, and then these cells were treated with different concentrations of CoQ10 with or without H 2 O 2 . Tartrate-resistant acid phosphatase staining was performed to detect osteoclasts. Cell viability was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, cell apoptosis was examined by flow cytometry, and the effects of CoQ10 on protein and messenger RNA expression of mitochondrial apoptosis-associated proteins and osteoclast marker proteins were measured by quantitative reverse transcription polymerase chain reaction and western blot, respectively. Furthermore, enzyme-linked immunosorbent assay was conducted to analyze the activities of malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT). RANKL significantly induced osteoclastogenesis in RAW264.7 cells, with the greatest efficiency at 50 ng/ml. CoQ10 had no significant effects on cell viability but it significantly increased the percentages of cell apoptosis. Mechanically, CoQ10 statistically decreased the levels of Bcl-2 and cytochrome C in mitochondria and upregulated the levels of Bax, cleaved caspase 3, and cytochrome C in the cytoplasm. Moreover, CoQ10 significantly decreased RANKL-induced osteoclastogenesis regardless of exposure to H 2 O 2 . In addition, CoQ10 statistically reduced MDA activity and elevated the activities of SOD and CAT, as well as the expression of oxidative stress-related proteins. CoQ10 may inhibit RANKL-induced osteoclastogenesis by regulation of mitochondrial apoptosis and oxidative stress in RAW264.7 cells. Highlights 1 Osteoclastic are efficiently differentiated at 50 ng/ml of RANKL in RAW264.7 cells. 2 Coenzyme Q10 (CoQ10) promotes mitochondrial apoptosis in RANKL-treated RAW264.7 cells. 3 CoQ10 inhibits mitochondrial oxidative stress in RANKL-treated RAW264.7 cells. 4 CoQ10 inhibits RANKL-induced osteoclastogenesis.
研究领域:
药理学
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细胞生物学
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骨质疏松症
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2024
·
IF 5.3
Yue Shan,Yu Jin,Xiaoqi Zhang,Yufei Tang,Wenli Lai,Jinfeng Liao,Mengjie Wu,Hu Long
The prolonged duration of orthodontic treatment remains a significant concern for both orthodontists and patients. In this study, we developed a degradable microneedle (MN) patch composed of hyaluronic acid (HA) and sodium alginate (SA) for the delivery of receptor activator of nuclear factor-kappa B ligand (RANKL) to accelerate tooth movement. This MN patch that was crosslinked by calcium chloride (CaCl 2 ) exhibited adequate mechanical properties and favorable in vitro mucosal insertion ability. Moreover, the MN patch can achieve sustained release of RANKL and maintain the biological stability of RANKL protein after one month of storage at −20 °C, 4 °C, or 37 °C. In vitro experiments using RAW 264.7 cells indicated that the HA/SA/RANKL MN possessed excellent biocompatibility and could effectively induce osteoclast differentiation. In vivo application of the HA/SA/RANKL MN in rat models showed a remarkable effect in promoting osteoclast formation and accelerating tooth movement. These findings suggest that the degradable HA/SA/RANKL MN holds significant potential for enhancing tooth movement efficiency.
研究领域:
口腔医学
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生物材料学
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药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2021
·
IF 4.451
Shan Shan Qi,Meng Li Shao,Ze Sun,Si Min Chen,Ying Jun Hu,Hong Tao Wang,Tian Kuo Wei,Xing Sheng Li,Hong Xing Zheng
Diabetic osteoporosis (DOP) is one of the complications of diabetes, with high morbidity, and high disability rate. Here, we established a diabetic rat model and administered lycopene to observe its effect on DOP. Our results showed that ten weeks lycopene treatment lowered blood glucose, improved diabetic induced polydipsia, overeating and body weight loss. Lycopene treatment also enhanced bone mineral density, restored bone mechanical and bone Micro-CT parameters of diabetic rats. Subsequently, lycopene decreased serum inflammatory cytokines levels and increased serum anti-oxidant indicators levels. Moreover, lycopene reduced the number of bone marrow adipocytes, and osteoclasts numbers of diabetic rats. The serum bone turnover markers levels were down-regulated after lycopene treatment. Meanwhile, the bone and serum OPG, RUNX 2 expression levels were up-regulated by lycopene in diabetic rats, and the OPG/RANKL ratio was also up-regulated. This study showed that lycopene could ameliorate diabetic induced bone loss via anti-inflammatory, anti-oxidation, and increasing OPG/RANKL ratio in diabetic rats. Lycopene could be used for nutritional intervention in patients with diabetic osteoporosis.
研究领域:
内分泌学
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营养学
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药理学
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骨科学
✓ 已验证
产品关联
DOI
高影响因子
Regenerative Biomaterials
·
2020
·Vol. 7
·期 3
·303-311
·
IF 4.882
Huang Deqiu,Zhao Fujian,Gao Wendong,Chen Xiaofeng,Guo Zhouyi,Zhang Wen
Strontium-substituted bioactive glass (Sr-BG) has shown superior performance in bone regeneration. Sr-BG-induced osteogenesis has been extensively studied; however, Sr-BG-mediated osteoclastogenesis and the underlying molecular mechanism remain unclear. It is recognized that the balance of osteogenesis and osteoclastogenesis is closely related to bone repair, and the receptor activators of nuclear factor kappaB ligand (RANKL) signaling pathway plays a key role of in the regulation of osteoclastogenesis. Herein, we studied the potential impact and underling mechanism of strontium-substituted sub-micron bioactive glass (Sr-SBG) on RANKL-induced osteoclast activation and differentiation in vitro. As expected, Sr-SBG inhibited RANKL-mediated osteoclastogenesis significantly with the experimental performance of decreased mature osteoclasts formation and downregulation of osteoclastogenesis-related gene expression. Furthermore, it was found that Sr-SBG might suppress osteoclastogenesis by the combined effect of strontium and silicon released through inhibition of RANKL-induced activation of p38 and NF-κB pathway. These results elaborated the effect of Sr-SBG-based materials on osteoclastogenesis through RANKL-induced downstream pathway and might represent a significant guidance for designing better bone repair materials.
研究领域:
生物材料
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骨生物学
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细胞信号
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2020
·
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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MEDIATORS OF INFLAMMATION
·
2017
·
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
BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH
·
2024
·
IF 1.9
Zheng Delu,Cui Chenli,Ye Chengsong,Shao Chen,Zha Xiujing,Xu Ying,Liu Xu,Wang Can
Coenzyme Q10 (CoQ10) is a potent antioxidant that is implicated in the inhibition of osteoclastogenesis, but the underlying mechanism has not been determined. We explored the underlying molecular mechanisms involved in this process. RAW264.7 cells received receptor activator of NF-κB ligand (RANKL) and CoQ10, after which the differentiation and viability of osteoclasts were assessed. After the cells were treated with CoQ10 and/or H2O2 and RANKL, the levels of reactive oxygen species (ROS) and proteins involved in the PI3K/AKT/mTOR and MAPK pathways and autophagy were tested. Moreover, after the cells were pretreated with or without inhibitors of the two pathways or with the mitophagy agonist, the levels of autophagy-related proteins and osteoclast markers were measured. CoQ10 significantly decreased the number of TRAP-positive cells and the level of ROS but had no significant impact on cell viability. The relative phosphorylation levels of PI3K, AKT, mTOR, ERK, and p38 were significantly reduced, but the levels of FOXO3/LC3/Beclin1 were significantly augmented. Moreover, the levels of FOXO3/LC3/Beclin1 were significantly increased by the inhibitors and mitophagy agonist, while the levels of osteoclast markers showed the opposite results. Our data showed that CoQ10 prevented RANKL-induced osteoclastogenesis by promoting autophagy via inactivation of the PI3K/AKT/mTOR and MAPK pathways in RAW264.7 cells.
研究领域:
细胞生物学
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分子生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Research
·
2024
·
IF 9.5
Li Xiaoqun,Kou Yufang,Jia Jia,Liu Minchao,Gao Runze,Li Yuhong,Li Gang,Xu Shuogui,Song Wei,Xie Yang,Li Xiaomin,Zhao Tiancong
The excessive reactive oxygen species (ROS) accumulation and overactivated osteoclastogenesis in subchondral bone has proved to be a major cause of osteoarthritis (OA). Scavenging of ROS microenvironment to inhibit the osteoclastogenesis is highly valued in the therapeutic process of osteoarthritis. Despite the excellent ability of polyphenolic colloidal to scavenge reactive oxygen species and its affinity for macrophages, the preparation of polyphenolic colloidal nanoparticles is limited by the complex intermolecular forces between phenol molecules and the lack of understanding of polymerization/sol-gel chemistry. Herein, our work introduces a novel poly-tannin-phenylboronic colloidal nanoparticle (PTA) exclusively linked by ROS-responsive bondings. Nanocolloidal PTA has a uniform particle size, is easy and scalable to synthesize, has excellent scavenging of ROS, and can be slowly degraded. For in vitro experiments, we demonstrated that, PTA could eliminate ROS within RAW264.7 cells and impede osteoclastogenesis and bone resorption. RNA sequencing results of PTA-treated RAW264.7 cells further reveal the promotion of antioxidant activity and inhibition of osteoclastogenesis. For in vivo experiments, PTA could eliminate the ROS environment and reduce the number of osteoclasts in the subchondral bone, thereby alleviating the damage of subchondral bone and symptoms of osteoarthritis. Our research, by delving into the formation of polyphenol colloidal nanoparticles and validating their role in ROS scavenging to inhibit osteoclastogenesis in subchondral bone, may open new avenues for OA treatment in the future.
研究领域:
纳米技术
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生物材料
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骨科
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
Biomaterials Science
·
2018
·Vol. 7
·期 3
·1101-1116
·
IF 5.831
Ting-ben Huang,Yong-zheng Li,Ke Yu,Zhou Yu,Ying Wang,Zhi-wei Jiang,Hui-ming Wang,Guo-li Yang
Bone remolding involves the formation of new bone by osteoblasts and the absorption of old bones by osteoclasts. Due to the vital role of osteoblasts and osteoclasts during bone regeneration, it might be feasible to promote osseointegration around the titanium implants by stimulating osteoblasts and inhibiting osteoclasts by modifying the surfaces of the implants. Lithium is used in the treatment of psychiatric patients, and it may be associated with osteogenesis. In this study, lithium was incorporated with sandblasted, large-grit and acid-etched titanium implants via a hydrothermal treatment. In vitro, the nano-scale surface enhanced the adhesion and proliferation of bone marrow mesenchymal stem cells (BMSCs). Moreover, the SLA-Li surface displayed a negative effect on the process of osteoclastogenesis. Further mechanism analysis indicated that the canonical Wnt/β-catenin signaling pathway was activated according to the results of RT-PCR and western blotting. More importantly, the RANKL/OPG signaling axis was also involved in these effects on the SLA-Li surface. The experiments in vivo proved that the SLA-Li surface could induce the bone formation and osseointegration during the early osseointegration after the dental implant surgery. These results suggested that bone homeostasis could be manipulated by an SLA-Li surface, which implied that this new surface might serve as a promising material for clinical application in the future.
研究领域:
生物材料
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组织工程
·
骨科
·
牙科种植学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2025
·
IF 2.2
XiaoRong Meng,Dandan Meng,Chenhui Xiang,Lingling Pu,Xiaofei Yin,Jing Yang
Objective Postmenopausal osteoporosis (PMOP) is a prevalent metabolic bone disorder characterized by decreased bone mineral density and an increased risk of fractures. This study aims to investigate the molecular mechanisms underlying the therapeutic effects of Apelin-13 in PMOP. Methods A PMOP model was established using mouse embryonic pre-osteoblast MC3T3-E1 cells treated with dexamethasone (DEX). A variety of experimental techniques—including MTT assays, Western blotting, flow cytometry, immunofluorescence staining, mitochondrial membrane potential assays, and ELISA—were employed to elucidate the potential mechanisms through which Apelin-13 exerts its therapeutic effects. Results Apelin-13 significantly enhanced osteoblast activity and effectively reversed the inhibitory effects of DEX on cell proliferation. It suppressed apoptosis by modulating the expression of apoptosis-related proteins. Furthermore, Apelin-13 promoted osteogenic differentiation, upregulated osteogenic protein expression, increased alkaline phosphatase (ALP) activity, and facilitated calcium nodule formation. It also improved mitochondrial function by reducing levels of reactive oxygen species (ROS) and malondialdehyde (MDA), boosting antioxidant enzyme activity, and activating the Nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathway. Critically, Apelin-13 was found to regulate the OPG/RANK/RANKL/IGF-1 signaling axis, and its pro-osteogenic effects were significantly enhanced when used in combination with SPA0355. Conclusion Apelin-13 exhibits promising therapeutic potential for PMOP in in vitro models by modulating key processes related to bone metabolism. It achieves this by attenuating mitochondrial oxidative phosphorylation and regulating the OPG/RANK/RANKL/IGF-1 pathway, thereby laying a foundation for future in vivo studies and clinical applications.
研究领域:
骨生物学
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内分泌代谢病学
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分子药理学
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细胞信号转导
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氧化应激与抗氧化
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骨骼系统疾病
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转化医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2024
·
IF 6.9
Tingting Chen,Gaoxiang Ai,Guihong Liang,Lingfeng Zeng,Di Zhao,Jun Liu,Yaoxing Dou
Inflammatory bowel disease is linked to a higher occurrence of bone loss. Oxyberberine can effectively improve experimental inflammatory bowel disease. However, no study has shown the effect of oxyberberine on inflammatory bowel disease induced bone loss. The present study was performed to investigate the role of oxyberberine in inflammatory bowel disease induced osteoporosis in chronic inflammatory bowel disease mice model. The inflammatory bowel disease mice were orally given two doses of oxyberberine daily. Blood, colon, and bone specimens were collected for biomarker assessments and histological examinations. Bone biomechanical properties and key proteins and genes involved in the receptor activator of nuclear factor kappa-B ligand/nuclear factor kappa-B signaling pathway were evaluated. Additionally, the binding characteristics of oxyberberine and receptor activator of nuclear factor kappa-B ligand were evaluated by in silico simulation. Results indicated that oxyberberine treatment significantly attenuated the macroscopic damage, colonic shortening, and histological injury from the colon. Furthermore, oxyberberine decreased serum inflammatory cytokine levels. The intervention with oxyberberine significantly mitigated the deterioration of bone mass, biomechanical properties, and microstructural parameters. Moreover, the upregulated osteoclast formation factors in model mice were significantly abolished by oxyberberine. In silico simulation results also showed that oxyberberine was firmly bound with target protein. Hence, our findings indicated that oxyberberine had the potential to mitigate inflammatory bowel disease induced inflammation in bone, inhibit osteoclast formation through regulating the receptor activator of nuclear factor kappa-B ligand/nuclear factor kappa-B signaling pathway, and might be a valuable approach in preventing bone loss associated with inflammatory bowel disease.
研究领域:
药理学
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免疫学
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骨骼生物学
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胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COMPOSITES PART B-ENGINEERING
·
2025
·
IF 14.2
Dongping Wang,Jiamin Yang,Chang Liu,Wei Lin,Shenglin Lei,Yuxian Chen,Pinying Cheng,Yilin Huang,Shuling Gu,Haishan Li,Yuewei Lin,Huizhi Guo,Guoye Mo,Bing Mai,Zheng Zhang,Qingtao Li,Yongxian Li,Xiaodong Cao,Shuncong Zhang
Osteoporosis (OP) is characterized by diminished bone mass and increased skeletal fragility, representing a metabolic disorder. Osteoporotic bone defects (OBD) pose significant treatment challenges due to the active generation of osteoclasts (OCs) and the suppression of osteogenic differentiation. These complications impose a substantial burden on patients and the healthcare system. To address this issue, alendronate sodium (AS) was incorporated into Gelatin methacryloyl (GelMA), and then loaded with ligustrum officinale polysaccharide (LOP) to form GelMA-AS-LOP microspheres. These multifunctional hydrogel microspheres, characterized by their abundant void structures, offered continuous drug release. GelMA-AS-LOP suppressed OCs’ activity and formation, enhanced osteogenic differentiation and mineralization, and exhibited low visceral toxicity. Consequently, they ameliorated the pathological microenvironment associated with OP and facilitate OBD regeneration. The hydrogel microspheres achieved this by promoting osteogenesis and modulating the NFATc1, RANKL (via LOP), and MAPK (via AS) signaling pathways, resulting in a dual synergistic effect.
研究领域:
生物材料
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组织工程
·
骨再生
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药理学
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细胞信号传导
✓ 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）