BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2025
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IF 2.2
Liting Wen,Xiaoxia Zeng,Zengping Lin,Peixiong Chen,Dapeng Zhao,Xianhai Zeng
Background Cholesteatoma is a benign epithelial lesion that affects the middle ear or mastoid process, causing otorrhea and hearing impairment. Currently, the pathogenesis of temporal bone injury in middle ear cholesteatoma remains elusive, hindering the development of effective treatment strategies. Methods and Results We examined the expression of transcription factor AP-2-beta (TFAP2B) and its downstream factor silent mating type information regulation 2 homolog 1 (SIRT1) in clinical samples from patients with middle ear cholesteatoma and analyzed the potential correlation between TFAP2B expression and clinical conditions. The findings revealed a significant down-regulation of TFAP2B and SIRT1 in patients diagnosed with middle ear cholesteatoma ( p < 0.01), and TFAP2B expression was negatively correlated with the clinical manifestations of hearing impairment and bone destruction. We further explored the role of TFAP2B in the differentiation of RAW 264.7 cells into osteoclasts induced by receptor activator of nuclear factor kappa B ligand (RANKL) in vitro . TFAP2B overexpression significantly inhibited, while TFAP2B knockdown promoted osteoclast differentiation of RAW264.7 cells. Further investigation suggested that TFAP2B positively regulated SIRT1 ( p <0.01) and negatively regulated NF-κB activation. Finally, we demonstrated that TFAP2B transcriptionally regulated SIRT, which inhibited the activation of the NF-κB signaling pathway by reducing the acetylation level of the p65 subunit, thereby suppressing osteoclast differentiation. Conclusions TFAP2B/SIRT1 plays a crucial role in regulating osteoclast differentiation in middle ear cholesteatoma. The downregulation of TFAP2B/SIRT1 triggers enhanced osteoclast differentiation, which may contribute to one of the mechanisms underlying bone destruction in middle ear cholesteatoma.
研究领域:
医学
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分子生物学
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DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2025
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IF 6.1
Jiaxiang Zhang,Haitao Ma,Yongjie Yang,Liyin Liu,Dasheng Luo,Defu Yu,Tao Chen
Excessive intake of essential and toxic metals affects the pathological process of osteoporosis. At present, the effects of single forms of iron (Fe), lead (Pb) and other metals on bone injury have been widely studied. However, these metal elements usually do not exist in the environment in a separate form. They are ingested in various ways and are often found together in the human body. However, the mechanism of bone damage caused by Fe and Pb mixed exposure is still unclear at this stage. At present, the combined analysis of multi-omics is the conventional method to explore the molecular mechanism behind the disease. Therefore, we attempted to combine proteomics and metabolomics to explain the mechanism of bone damage caused by mixed Fe and Pb exposure. Differential proteins and metabolites were found to be predominantly enriched in the JAK-STAT signalling pathway, inflammatory bowel disease (IBD), and osteoclast differentiation. Combined analysis showed that Fpr2, Lifr, Lisofylline, 7-Ketocholesterol, LacCer (d18: 1/14:0) and other substances may be involved in the process of bone injury mediated by mixed metal exposure. In summary, we hypothesise that mixed exposure to Fe and Pb leads to osteoclast activation via the JAK-STAT signalling pathway in situ and indirectly via the gut-bone axis, resulting in bone damage. In general, our study potentially suggests that bone injury induced by mixed exposure of Fe and Pb may be related to osteoclast proliferation mediated by changes in inflammatory levels in vivo .
研究领域:
分子生物学
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毒理学
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骨代谢研究
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PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
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2020
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IF 3.347
Haoyi Zheng,Haitao Feng,Wenzhong Zhang,Yantao Han,Wenwen Zhao
With the growth of the aging population, osteoporosis is becoming a global health problem. Ursolic acid (UA) is an active ingredient existed in a variety of foods and nature plants and owns plenty of pharmacological effects especially in treating metabolic disease . Our predication from network pharmacology hinted that UA has potential for ameliorating osteoporosis. Firstly through in vivo experiment, we confirmed that UA administration obviously protected against ovariectomy (OVX)-induced osteoporosis in rats by improving microarchitectural deterioration of trabecular bone ( P < 0.001), decreasing numbers of TRAP positive osteoclast in vertebra ( P < 0.001), as well as decreasing serum osteoclast-specific cytokines release ( P < 0.001). Besides, UA ameliorated kidney damage secondary to OVX-induced osteoporosis by ameliorating glomerular atrophy, decreasing BUN and creatinine levels in OVX rats. In vitro , UA noticeably decreased osteoclastic-special marker proteins c-Fos and NFATc1 expressions ( P < 0.001) in response to RANKL stimulation in macrophagy. Importantly, autophagy pathway was activated in the process of osteoclast differentiation and blocked by UA pretreatment . Furthermore, autophagy inhibitors suppressed osteoclast differentiation ( P < 0.001). Collectively, UA may ameliorate osteoporosis by suppressing osteoclast differentiation mediated by autophagy. Our research provides scientific support for UA treating osteoporosis and offers an optimal dose for daily intake of UA safely to prevent bone diseases.
研究领域:
药理学
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老年医学
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骨骼生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2023
·Vol. 24
·期 10
·8682
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IF 5.6
Zijiao Zhang,Juhan Song,Seung-Hee Kwon,Zhao Wang,Suk-Gyun Park,Xianyu Piao,Je-Hwang Ryu,Nacksung Kim,Ok-Su Kim,Sun-Hun Kim,Jeong-Tae Koh
There has been increasing interest in adjunctive use of anti-inflammatory drugs to control periodontitis. This study was performed to examine the effects of pirfenidone (PFD) on alveolar bone loss in ligature-induced periodontitis in mice and identify the relevant mechanisms. Experimental periodontitis was established by ligating the unilateral maxillary second molar for 7 days in mice (n = 8 per group), and PFD was administered daily via intraperitoneal injection. The micro-computed tomography and histology analyses were performed to determine changes in the alveolar bone following the PFD administration. For in vitro analysis, bone marrow macrophages (BMMs) were isolated from mice and cultured with PFD in the presence of RANKL or LPS. The effectiveness of PFD on osteoclastogenesis, inflammatory cytokine expression, and NF-κB activation was determined with RT-PCR, Western blot, and immunofluorescence analyses. PFD treatment significantly inhibited the ligature-induced alveolar bone loss, with decreases in TRAP-positive osteoclasts and expression of inflammatory cytokines in mice. In cultured BMM cells, PFD also inhibited RANKL-induced osteoclast differentiation and LPS-induced proinflammatory cytokine (IL-1β, IL-6, TNF-a) expression via suppressing the NF-κB signal pathway. These results suggest that PFD can suppress periodontitis progression by inhibiting osteoclastogenesis and inflammatory cytokine production via inhibiting the NF-κB signal pathway, and it may be a promising candidate for controlling periodontitis.Keywords:pirfenidone;periodontitis;osteoclast differentiation;alveolar bone loss;inflammation;NF-κB pathway
研究领域:
牙科学
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药理学
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免疫学
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DOI
PubMed
高影响因子
iScience
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2025
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IF 4.1
Pan Liu,Jiezhong Deng,Yusheng Yang,Wenxi Bai,Shengtao Dong,Zehua Zhang
Tuberculosis (TB), caused by Mycobacterium tuberculosis ( M.tb ), is one of the most ancient diseases recorded. In cases of bone TB, it significantly disrupts bone homeostasis, though the precise mechanisms are poorly understood and effective treatment targets are scarce. Our study investigated the role of Rv1509 in the pathogenesis of bone TB. We found that Rv1509 enhances the differentiation of bone marrow macrophages (BMMs) into osteoclasts by activating the TLR2 pathway, which stimulates the production of IL-6 and TNF-α. This, in turn, indirectly inhibits osteoblast differentiation and mineralization. Additionally, Rv1509 directly impairs osteoblast function and enhances the secretion of RANKL via TLR2 signaling, creating a detrimental RANKL/OPG imbalance that promotes osteoclast differentiation and bone degradation. Notably, the injection of Rv1509 into mouse skulls led to extensive bone damage, highlighting its significant role as a virulence factor in the pathogenesis of bone TB.
研究领域:
免疫学
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微生物学
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骨骼生物学
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DOI
PubMed
高影响因子
Gels
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2025
·Vol. 11
·期 2
·112
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IF 5.3
Beibei Wu,Xiaoqiu Dou,Sravan Baddi,Fengli Gao,Changli Zhao,Chuanliang Feng
Osteoporosis, a chronic bone disorder, poses a global threat to the health of millions of individuals. The disruption of bone homeostasis is the fundamental cause of osteoporosis. Currently, clinical drugs are employed to promote bone formation via enhancing osteogenesis and/or reduce bone loss via inhibiting osteoclastogenesis. However, it is difficult for the current drugs to simultaneously address the osteoblastogenesis and osteoclastogenesis issues associated with osteoporosis. Hence, L/D-phenylalanine derivatives (L/DPF), combined with Mg2+ions, are employed to assemble into chiral supramolecular hydrogels which facilitate osteocyte activity and inhibit osteoclast function. LPF_Mg hydrogels and DPF_Mg hydrogels demonstrate the opposite supramolecular chirality. Specifically, LPF_Mg hydrogels and DPF_Mg hydrogels are composed of left-handed (M-type) helical nanofibers and right-handed (P-type) helical nanofibers, respectively. The hydrogen bonding and π–π stacking interactions are crucial in the process of hydrogel formation. The chiral left-handed nanofibrous DPF_Mg hydrogels significantly promote osteogenic differentiation of MC3T3 cells and inhibit osteoclast differentiation of RAW267.4 cells, thereby demonstrating substantial potential for applications in improving skeletal health. These findings provide a promising novel perspective on the application of chiral functional materials for osteoporosis therapy.
研究领域:
生物材料学
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骨生物学
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医学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF HISTOCHEMISTRY
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2023
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IF 2
Jing Guo,Chang-Yong Tong,Jian-Guang Shi,Xin-Jian Li,Xue-Qin Chen
Lung cancer is prone to bone metastasis, and osteopontin (OPN) has an important significance in maintaining bone homeostasis. The goal of this study was to explore the impact of OPN level on bone metabolism and the molecular mechanism of inhibiting bone metastasis in non-small cell lung cancer (NSCLC). The expression of OPN in NSCLC was ascertained by Western blot and immunohistochemistry, and the correlation between the expression level of OPN and survival of patients was analyzed. Then the shRNA technology was applied to reduce the expression of OPN in NSCLC cells, and CCK-8 assay was carried out to investigate the effect of low expression of OPN on the proliferation of NSCLC cells. In addition, the effects of low expression of OPN on osteoclast differentiation, osteoblast generation and mineralization were studied using osteoclast precursor RAW264.7 and human osteoblast SaOS-2 cells, and whether OPN could regulate miR-34c/ Notch pathway to affect bone metabolism was further explored. The findings showed that the high level of OPN in NSCLC was closely related to the poor prognosis of patients and the abnormal proliferation of NSCLC cell lines. The suppression of OPN was beneficial to inhibit the differentiation of osteoclasts and promote the mineralization of osteoblasts. Besides, this study confirmed that the deletion of OPN can regulate bone metabolism through the regulation of miR-34c/Notch1 pathway, which will contribute to inhibiting the occurrence of osteolytic bone metastasis in NSCLC.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
PLoS One
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2023
·Vol. 18
·期 2
·e0281845
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IF 3.7
Hao Tang,Shida Zhu,Kai Chen,Shujie Yuan,Junzu Hu,Hongkai Wang
Bone is a frequent target of tumor metastasis, with high incidence rate and poor prognosis. Osteoclasts play a key role in the process of tumor bone metastasis. Interleukin-17A (IL-17A) is an inflammatory cytokine, highly expressed in a variety of tumor cells, that can alter the autophagic activity of other cells, thereby causing corresponding lesions. Previous studies have shown that low concentration IL-17A can promote osteoclastogenesis. The aim of this study was to clarify the mechanism of low concentration IL-17A promoting osteoclastogenesis by regulating autophagic activity. The results of our study showed that IL-17A could promote the differentiation of osteoclast precursors (OCPs) into osteoclasts in the presence of RANKL, and increase the mRNA levels of osteoclast-specific genes. Moreover, IL-17A increased the expression of Beclin1 by inhibiting the phosphorylation of ERK and mTOR, leading to enhanced autophagy of OCPs, accompanied by decreased OCP apoptosis. Furthermore, knockdown of Beclin1 and suppression of autophagy by 3-methyladenine (3-MA) significantly attenuated the enhanced osteoclastogenesis induced by IL-17A. In summary, these results indicate that low concentration IL-17A enhances the autophagic activity of OCPs through the ERK/mTOR/Beclin1 pathway during osteoclastogenesis, and further promotes osteoclast differentiation, suggesting that IL-17A may serve as a potential therapeutic target for cancer-related bone resorption in cancer patients.
研究领域:
肿瘤学
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免疫学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
Molecular Medicine Reports
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2023
·Vol. 29
·期 2
·1-11
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IF 3.4
Xiaoqian Guo,Guangwei Qiao,Jingjiao Wang,Changyi Yang,Min Zhao,Qian Zhang,Yingbiao Wan
Diabetic periodontitis (DP) refers to destruction of periodontal tissue and absorption of bone tissue in diabetic patients. Tumor necrosis factor receptor‑associated factor (TRAF)‑interacting protein with forkhead‑associated domain (TIFA) as a crucial regulator of inflammation activates the NF‑κB signaling pathway to regulate cell biological behavior. However, the function and mechanism of TIFA on DP suffer from a lack of research. In the present study, TIFA was upregulated in the periodontal tissue of a DP mouse model. In addition, the expression of TIFA in RAW264.7 cells was induced by high glucose (HG) culture and increased by lipopolysaccharide (LPS) from Porphyromonas gingivalis treatment in a time‑dependent manner. Knockdown of TIFA significantly reduced the levels of inflammatory cytokines, including TNF‑α, IL‑6, IL‑1β and monocyte chemoattractant protein‑1, in HG and LPS‑induced RAW264.7 cells. The nuclear translocation of NF‑κB p65 was induced by HG and LPS and was clearly suppressed by absence of TIFA. The expression of downstream factors Nod‑like receptor family pyrin domain‑containing 3 and apoptosis‑associated speck‑like protein was inhibited by silencing TIFA. Moreover, TIFA was increased by receptor activator of NF‑κB (RANK) ligand (RANKL) in a concentration dependent manner. The expression of cathepsin K, MMP9 and nuclear factor of activated T cells cytoplasmic 1 was downregulated by depletion of TIFA. RANKL‑induced osteoclast differentiation was inhibited by silencing of TIFA. Meanwhile, the decrease of TIFA blocked activation of the NF‑κB pathway in RANKL‑treated RAW264.7 cells. In conclusion, TIFA as a promoter regulates the inflammation and osteoclast differentiation via activating the NF‑κB signaling pathway.
研究领域:
牙科
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分子生物学
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免疫学
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DOI
PubMed
高影响因子
ORAL DISEASES
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2023
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IF 3.8
Shiqun Sun,Tongtong Yan,Nan Yang,Jian Wu,Zhihui Liu
Objectives The aim of this study was to explore the potential role of zinc-finger homeodomain transcription factor (TCF8) in osteoclastogenesis and inflammation during periodontitis. Materials and Methods Rats with periodontitis were induced via Porphyromonas gingivalis -lipopolysaccharide (Pg-LPS) injection. The recombinant lentivirus delivering short hairpin RNA (shRNA) against TCF8 was used to downregulate TCF8 in vivo. Alveolar bone loss in rats was determined by micro-computed tomography (Micro-CT). Typical pathological changes, periodontal tissue inflammation, and osteoclastogenesis were evaluated via histological analyses. The RAW264.7-derived osteoclasts were induced by RANKL stimulation. TCF8 downregulation in vitro was achieved by lentivirus infection. The osteoclast differentiation and inflammatory signaling in RANKL-induced cells were measured via immunofluorescence methods and molecular biology approaches. Results Porphyromonas gingivalis -lipopolysaccharide induced rats exhibited overexpressed TCF8 in their periodontal tissues, while TCF8 knockdown attenuated the bone loss, tissue inflammation, and osteoclastogenesis in LPS-induced rats. Besides, TCF8 silencing inhibited RANKL-induced osteoclast differentiation in RAW264.7 cells, as evidenced by the reduced numbers of TRAP-positive osteoclasts, less formation of F-actin rings, and downregulated expressions of osteoclast-specific markers. It also exerted an inhibitory effect on the NF-κB signaling in RANKL-induced cells via blocking NF-κB p65 phosphorylation and nuclear translocation. Conclusions TCF8 silencing inhibited alveolar bone loss, osteoclast differentiation, and inflammation in periodontitis.
研究领域:
牙科学
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分子生物学
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炎症
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转录因子
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骨骼生物学
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PubMed
高影响因子
CELL PROLIFERATION
·
2020
·Vol. 54
·期 1
·e12955
·
IF 5.753
Jun Ma,Lei Zhu,Zhibin Zhou,Tengfei Song,Lei Yang,Xu Yan,Aimin chen,Tian Wen Ye
Objectives Calcium ion signals are important for osteoclast differentiation. Transient receptor potential vanilloid 6 (TRPV6) is a regulator of bone homeostasis. However, it was unclear whether TRPV6 was involved in osteoclast formation. Therefore, the aim of this study was to evaluate the role of TPRV6 in bone metabolism and to clarify its regulatory role in osteoclasts at the cellular level. Materials and methods Bone structure and histological changes in Trpv6 knockout mice were examined using micro-computed tomography and histological analyses. To investigate the effects of Trpv6 on osteoclast function, we silenced or overexpressed Trpv6 in osteoclasts via lentivirus transfection, respectively. Osteoclast differentiation and bone resorption viability were measured by tartrate-resistant acid phosphatase (TRAP) staining and pit formation assays. The expression of osteoclast marker genes, including cathepsin k, DC-STAMP, Atp6v0d2 and TRAP, was measured by qRT-PCR. Cell immunofluorescence and Western blotting were applied to explore the mechanisms by which the IGF-PI3K-AKT pathway was involved in the regulation of osteoclast formation and bone resorption by Trpv6. Results We found that knockout of Trpv6 induced osteoporosis and enhanced bone resorption in mice, but did not affect bone formation. Further studies showed that Trpv6, which was distributed on the cell membrane of osteoclasts, acted as a negative regulator for osteoclast differentiation and function. Mechanistically, Trpv6 suppressed osteoclastogenesis by decreasing the ratios of phosphoprotein/total protein in the IGF–PI3K–AKT signalling pathway. Blocking of the IGF–PI3K–AKT pathway significantly alleviated the inhibitory effect of Trpv6 on osteoclasts formation. Conclusions Our study confirmed the important role of Trpv6 in bone metabolism and clarified its regulatory role in osteoclasts at the cellular level. Taken together, this study may inspire a new strategy for the treatment of osteoporosis.
研究领域:
骨骼生物学
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细胞信号传导
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分子生物学
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药理学
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DOI
PubMed
高影响因子
EXPERIMENTAL CELL RESEARCH
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2022
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IF 4.145
Yanling Zhang,Zhiyun Du,Dan Li,Zhuo Wan,Tianyi Zheng,Xuehui Zhang,Yingjie Yu,Xiaoping Yang,Qing Cai
Due to the inflammatory responses associated with defect occurrence and materials implantation, immunoregulation has emerged as a promising strategy to enhance bone regeneration . It has been widely reported that a material could facilitate osteogenesis if it can guide macrophages to anti-inflammatory M2 phenotype, vice versa, a substrate will influence macrophage phenotype if it is osteoinductive. However, few studies have looked into the intercellular crosstalking directly. Herein, the compound catalpol was selected for its multiple functions to study the interactions between bone marrow mesenchymal stromal cells (BMSCs) and macrophages. This iridoid glucoside exhibits excellent anti-inflammatory and osteoinductive activities. The effects of catalpol on mediating M1/M2 polarization of macrophages, inhibiting osteoclast differentiation , promoting osteogenesis and angiogenesis were systematically investigated to correlate the biological responses of BMSCs and macrophages. To extend its in vivo application, the catalpol was then loaded onto an electrospun polylactide/gelatin composite fibrous mesh and subcutaneously implanted to evaluate the local inflammation and ectopic osteogenesis. The results revealed that the functions of catalpol displayed in modulating cellular behaviors are via cell paracrine to strengthen intercellular crosstalking, hence demonstrating that catalpol itself could serve as a promising bioactive stimulator for bone tissue engineering.
研究领域:
组织工程
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生物材料
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免疫学
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细胞生物学
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再生医学
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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）