BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2025
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IF 2.2
Qiuni Gao,Shangyu Zeng,Yupeng Chen,Ying Bao,Haiyan Cui
Alopecia, a prevalent condition driven by abnormal hair follicle cycling and stem cell (HFSCs) dysregulation, underscores the need to elucidate molecular mechanisms governing HFSCs activation. While the nuclear factor of activated T cells c1 (NFATc1) is known to maintain HFSCs quiescence by suppressing cyclin-dependent kinase 4 (CDK4), the upstream regulators of this pathway remain unclear. Here, we identify MafB as a key modulator of HFSCs dynamics through NFATc1 signaling. Transcriptome sequencing of murine skin revealed elevated MafB expression during active hair regeneration. Adenoviral overexpression of MafB in depilated mice accelerated hair regrowth, increased hair follicle diameter, and enhanced HFSCs proliferation. Conversely, MafB knockdown suppressed regeneration and reduced the prolifiration ability of HFSCs. In vitro , MafB overexpression promoted HFSCs proliferation, migration, and differentiation, while mechanistic studies demonstrated MafB inhibits NFATc1 transcription, thereby relieving CDK4 repression and activating Wnt/β-catenin signaling. Rescue experiments confirmed NFATc1 restoration abrogated MafB-induced HFSCs activation. These findings establish MafB as a critical regulator of hair follicle cycling through the NFATc1/CDK4 axis, offering novel therapeutic avenues for alopecia.
研究领域:
分子生物学
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发育生物学
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皮肤科学
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DOI
PubMed
高影响因子
Cell and Bioscience
·
2022
·Vol. 12
·期 1
·1-20
·
IF 9.584
Zhang Yufeng,Yang Min,Zhang Sheng,Yang Zhiqiang,Zhu Yufan,Wang Yi,Chen Zhe,Lv Xuan,Huang Zan,Xie Yuanlong,Cai Lin
Background Dysregulated osteoclast activity due to altered osteoclast differentiation causes multiple bone diseases. Osteoclasts are multinucleated giant cells derived from hematopoietic stem cells and play a major role in bone absorption. However, the mechanisms underlying the tight regulation of osteoclast differentiation in multiple pathophysiological status remain unknown. Results We showed that Bhlhe40 upregulation is tightly associated with osteoclast differentiation and osteoporosis. Functionally, Bhlhe40 promoted osteoclast differentiation in vitro, and Bhlhe40 deficiency led to increased bone mass and decreased osteoclast differentiation in vivo. Moreover, Bhlhe40 deficient mice resisted estrogen deficiency and aging-induced osteoporosis. Mechanism study showed that the increase in bone mass due to Bhlhe40 deficiency was a cell intrinsic defect in osteoclast differentiation in these mice. BHLHE40 upregulated the gene expression of Fos and Nfatc1 by directly binding to their promoter regions. Notably, inhibition of Fos/Nfatc1 abrogated the enhanced osteoclast differentiation induced by BHLHE40 overexpression. Conclusions Our research reveals a novel Bhlhe40/c-Fos/Nfatc1 axis involved in regulating osteoclastogenesis and shows that osteoporosis caused by estrogen deficiency and aging can be rescued by regulating Bhlhe40 in mice. This may help in the development of a new strategy for the treatment of osteoporosis.
研究领域:
骨骼生物学
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分子生物学
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病理生理学
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产品关联
DOI
PubMed
高影响因子
BIOCHIMIE
·
2018
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IF 3.188
Ji Li,Yanping Li,Shuang Pan,Lin Zhang,Lina He,Yumei Niu
Paeonol is a natural phenolic compound in Moutan Cortex with multiple biological functions, such as anti-inflammatory and anti-oxidant activity. Recent evidence has proven that persistent inflammation, oxidative stress , along with nuclear factor E2-related factor 2 (Nrf2) signaling dysfunction in periodontium are the possible causes of alveolar bone resorption , and ultimately lead to periodontitis. The present study was designed to explore the protective effects of paeonol on ligation-induced periodontitis in rats, and investigate the possible mechanism. We found that treatment with paeonol (40, 80 mg/kg, intraperitoneal injection) for 7 days remarkably decreased the expression of receptor activator of nuclear factor kappa-B ligand increased the expression of osteoprotegrin and inhibited the formation of osteoclasts . This function of paeonol might be correlated with its ability to reduce inflammatory factors (IL-1β, IL-6 and TNF-α) and alleviate oxidative stress (SOD, MDA, GSH and ROS) in gingival tissues. Besides, paeonol increased Nrf2 activity. Silence of Nrf2 using specific siRNA diminished the inhibitory effect of paeonol on NF-κB p65 activation and downstream expression, suggesting that Nrf2 was essential for protective effect of paeonol. These results showed that paeonol protected against periodontitis-aggravated osteoclastogenesis and alveolar bone lesion via regulating Nrf2/NF-κB/NFATc1 signaling pathway .
研究领域:
药理学
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牙医学
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分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
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IF 5.6
Yu Bai,Mi Tian,Ping He,Yongzhe Zhang,Jie Chen,Zixia Zhao,Jingsi Lan,Beiru Zhang
Prolonged renal inflammation contributes to fibrosis, which may eventually lead to irreversible chronic kidney disease. Our previous work demonstrated that LIM and cysteine-rich domain 1 (LMCD1) are associated with renal interstitial fibrosis in a 21-day unilateral ureteral obstruction (21UUO) mouse model. Interestingly, based on the gene expression omnibus database, we found that LMCD1 is enhanced in the mouse kidney as early as 5, 7, and 10 days following unilateral ureteral obstruction (UUO), suggesting that LMCD1 may exert its function in an earlier phase. To validate this conjecture, a 7UUO mouse model and a tumor necrosis factor-α (TNF-α)-stimulated HK-2 cell model were established, followed by injection of adenovirus vectors carrying short hairpin RNA targeting LMCD1. LMCD1 silencing ameliorated renal collagen deposition and reduced the expression of profibrotic factors in the 7UUO model. LMCD1 silencing alleviated tubulointerstitial inflammation by mitigating F4/80 + cell infiltration, monocyte chemoattractant protein-1 release and nuclear factor-κB activation. In addition, LMCD1 silencing suppressed NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation and nuclear factor of activated T cells 1 (NFATc1) nuclear translocation. Consistent results were obtained in TNF-α-stimulated HK-2 cells in vitro . Mechanistically, the transcriptional coactivator LMCD1 cooperates with the transcription factor NFATc1 to increase NLRP3 expression. Collectively, these findings suggest that LMCD1 participates in tubulointerstitial inflammation via an LMCD1-NFATc1/NLRP3 mechanism. LMCD1 may therefore become a potential target for the control of renal inflammation and fibrosis.
研究领域:
肾病学
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炎症
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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
Biomaterials Research
·
2023
·Vol. 27
·期 1
·1-15
·
IF 11.3
Shi Jiachen,Ma Qiuling,Su Wenting,Liu Congyan,Zhang Huangqin,Liu Yuping,Li Xiaoqi,Jiang Xi,Ge Chang,Kong Fei,Chen Yan,Qu Ding
Background Conventional dissolving microneedles (DMNs) face significant challenges in anti-melanoma therapy due to the lack of active thrust to achieve efficient transdermal drug delivery and intra-tumoral penetration.Methods In this study, the effervescent cannabidiol solid dispersion-doped dissolving microneedles (Ef/CBD-SD@DMNs) composed of the combined effervescent components (CaCO3 & NaHCO3) and CBD-based solid dispersion (CBD-SD) were facilely fabricated by the “one-step micro-molding” method for boosted transdermal and tumoral delivery of cannabidiol (CBD).Results Upon pressing into the skin, Ef/CBD-SD@DMNs rapidly produce CO2 bubbles through proton elimination, significantly enhancing the skin permeation and tumoral penetration of CBD. Once reaching the tumors, Ef/CBD-SD@DMNs can activate transient receptor potential vanilloid 1 (TRPV1) to increase Ca2+ influx and inhibit the downstream NFATc1-ATF3 signal to induce cell apoptosis. Additionally, Ef/CBD-SD@DMNs raise intra-tumoral pH environment to trigger the engineering of the tumor microenvironment (TME), including the M1 polarization of tumor-associated macrophages (TAMs) and increase of T cells infiltration. The introduction of Ca2+ can not only amplify the effervescent effect but also provide sufficient Ca2+ with CBD to potentiate the anti-melanoma efficacy. Such a “one stone, two birds” strategy combines the advantages of effervescent effects on transdermal delivery and TME regulation, creating favorable therapeutic conditions for CBD to obtain stronger inhibition of melanoma growth in vitro and in vivo.Conclusion sThis study holds promising potential in the transdermal delivery of CBD for melanoma therapy and offers a facile tool for transdermal therapies of skin tumors.
研究领域:
药学
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生物医学工程
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肿瘤学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2023
·Vol. 37
·期 4
·1422-1434
·
IF 7.2
Yanfei Ban,Yang Wang,Liming Qiao,Chengzhong Zhang,Hongrui Wang,Xuhui He,Dan Jia,Chengjian Zheng
The seeds of Vitex negundo have been used for inflammation-related disease treatment in traditional medicine. This study focused on the anti-osteoarthritis (OA) effects of the total lignans of V. negundo seeds (TOV) in monosodium iodoacetate-induced osteoarthritis rats and its pharmacokinetic properties, as well as the effects and potential mechanism of its main components VN1 (6-hydroxy-4-(4-hydroxy-3-methoxy-phenyl)-3-hydro-xymethyl-7-methoxy-3,4-dihydro-2-naphthaldehydeb) and VN2 (vitedoin A) on receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation in bone marrow macrophages (BMMs). TOV significantly attenuated osteoarthritis, leading to an increase in pain thresholds, improvement of knee articular cartilages and chondrocytes loss, and decreased total joint scores and serum levels of TNF-α, interleukin-1β (IL-1β), and prostaglandin E2 (PGE2) in osteoarthritis rats. The half-time (T 1/2 ) was 2.82 h and 1.33 h, and the bioavailability was 15.34%–21.89% and 16.29%–22.11%, for VN1 and VN2, respectively. VN2, rather than VN1, remarkably inhibited tartrate-resistant acid phosphatase (TRAP) activity, reduced the number of TRAP-positive multinuclear cells, diminished the formation of actin ring, and decreased mRNA levels of cathepsin K (CTSK), TRAP, nuclear factor of activated T cell 1 (NFATc1), and osteoclast-associated receptor, as well as downregulated protein levels of p-ERK (phosphorylated extracellular signal-regulated kinase), TRAP, CTSK and NFATc1 in BMMs. These findings suggest TOV has promising therapeutic potential for OA treatment and VN2, in particular, attenuates osteoclast differentiation by suppressing ERK/NFATc1 signaling and actin ring, mainly accounting for the anti-OA efficacy of TOV.
研究领域:
药理学
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风湿病学
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传统医学
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分子生物学
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药代动力学
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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
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骨再生
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药理学
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细胞信号传导
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产品关联
DOI
高影响因子
Cell Reports
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2022
·
IF 9.995
Fanyuan Yu,Feifei Li,Peng Yu,Bin Zhou,Ling Ye
Summary Skeletal stem cells (SSCs) fuel adult bone with stemness resources to maintain homeostasis and support regeneration, which depends on the precise determination of the osteogenic lineage commitment of SSCs. In this study, using Cre-loxP reporter lineage tracking, we identified and characterized a population of NFATc1 + SSCs in bone regeneration. Pre-existing NFATc1 + SSCs are involved in early bone callus formation. Subsequently, these NFATc1 + SSCs produce osteolineage descendants in the subsequent stages of regeneration. The Ca 2+ -triggered transcriptional activity of NFATc1 constitutes the pre-imprinted memory of the trajectory to intrinsically orchestrate osteogenesis of SSCs. Inhibition of Ca 2+ /NFATc1 signaling in SSCs directly impairs osteogenesis and bone regeneration. In summary, our findings provide a mechanistic understanding of adult bone regeneration through the regulation of NFATc1 + SSCs.
研究领域:
干细胞生物学
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骨生物学
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再生医学
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DOI
PubMed
高影响因子
Theranostics
·
2021
·
IF 11.556
Lichan Yuan,Na Zhao,Junyi Wang,Yuying Liu,Li Meng,Shuyu Guo,Erik A.C. Wiemer,Qi Chen,Yelin Mao,Jingjing Ben,Junqing Ma
Rationale: Bone homeostasis is maintained by a balanced interplay of osteoblasts and osteoclasts. Osteoclasts are derived from monocyte/macrophage lineage. Major vault protein (MVP) is known to promote apoptosis and prevent metabolic diseases in macrophage. However, whether MVP is involved in osteoclastogenesis is unknown. Here, we identified an important function of MVP as a negative regulator of osteoclastogenesis and its therapeutic potential in preventing bone loss. Methods: Expression of MVP in osteoclasts was investigated in human tumor tissues with immunohistochemical staining. Next, we generated total body ( Mvp -/- ) and monocyte-specific ( Mvp f/f Lyz2-Cre ) MVP gene knockout mice to observe bone phenotype and osteoclastogenesis using micro-CT and bone histomorphometry. Moreover, we examined the effects of MVP on osteoclast differentiation, bone resorption, NFATc1 activation and calcium oscillations in vitro . Finally, we explored the clinical potential of targeting MVP in two osteoporosis mouse models and used an adeno-associated virus (AAV) gene to overexpress MVP locally in mice. Results: We found that Mvp -/- and Mvp f/f Lyz2-Cre mice both exhibited osteoporosis-like phenotypes. MVP-deficiency also enhanced calcineurin-NFATc1 signaling and promoted NFATc1 activity, which led to enhanced osteoclastogenesis and bone resorption. Calcineurin inhibition using the small molecule inhibitor FK506 corrected the enhanced osteoclastogenesis in Mvp f/f Lyz2-Cre group. Additionally, MVP reexpression in Mvp f/f Lyz2-Cre group rescued calcineurin expression. MVP overexpression in wild-type mice prevented pathologic bone loss in mouse models of ovariectomized (OVX) and calvaria-adjacent lipopolysaccharide (LPS)-injected. Conclusions: Our data suggested that MVP negatively regulates osteoclast differentiation and bone resorption via inhibition of calcineurin-NFATc1 signaling. In osteoclast-related bone diseases such as osteoporosis, manipulation of MVP activity may be an attractive therapeutic target.
研究领域:
骨骼生物学
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分子生物学
·
细胞信号传导
·
基因治疗
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2023
·
IF 5.6
Huang Yaxian,Wu Jinyan,Zhan Chi,Liu Rong,Zhou Zhaocai,Huang Xin,Tian Yaguang,Lin Zhengmei,Song Zhi
The enhanced osteoclastogenesis contributes to alveolar bone resorption in periodontitis, which increases the risk of tooth loss. To reduce bone destruction, the inhibition of osteoclast development is proposed as a feasible treatment. CD40L-CD40-TRAF6 signal transduction plays a crucial role in inflammation, but how it regulates osteoclast activity in periodontitis has not been elucidated. In this study, we showed the potential role of CD40L-CD40-TRAF6 signaling in periodontitis. CD40L obviously promoted osteoclast formation and bone resorption capacity in vitro. Mechanistically, we found that osteoclastogenesis was enhanced by the overexpression of NFATc1 and NF-κB activation. Importantly, osteoclast activity was effectively suppressed by TRAF-STOP, a small molecular inhibitor of TRAF6. Furthermore, local injection of TRAF-STOP-loaded injectable PLGA-PEG-PLGA hydrogel could alleviate ligation-induced periodontitis in vivo. Taken together, TRAF-STOP shows promising clinical efficacy in periodontitis through alleviating osteoclastogenesis.
研究领域:
牙科学
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免疫学
·
药理学
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产品关联
DOI
PubMed
高影响因子
International Journal of Oral Science
·
2020
·Vol. 12
·期 1
·1-10
·
IF 3.047
Zhang Ruilin,Li Junhui,Li Gongchen,Jin Fujun,Wang Zuolin,Yue Rui,Wang Yibin,Wang Xiaogang,Sun Yao
Activation of osteoclasts during orthodontic tooth treatment is a prerequisite for alveolar bone resorption and tooth movement. However, the key regulatory molecules involved in osteoclastogenesis during this process remain unclear. Long noncoding RNAs (lncRNAs) are a newly identified class of functional RNAs that regulate cellular processes, such as gene expression and translation regulation. Recently, lncRNAs have been reported to be involved in osteogenesis and bone formation. However, as the most abundant noncoding RNAs in vivo, the potential regulatory role of lncRNAs in osteoclast formation and bone resorption urgently needs to be clarified. We recently found that the lncRNA Nron (long noncoding RNA repressor of the nuclear factor of activated T cells) is highly expressed in osteoclast precursors. Nron is downregulated during osteoclastogenesis and bone ageing. To further determine whether Nron regulates osteoclast activity during orthodontic treatment, osteoclastic Nron transgenic (Nron cTG) and osteoclastic knockout (Nron CKO) mouse models were generated. When Nron was overexpressed, the orthodontic tooth movement rate was reduced. In addition, the number of osteoclasts decreased, and the activity of osteoclasts was inhibited. Mechanistically, Nron controlled the maturation of osteoclasts by regulating NFATc1 nuclear translocation. In contrast, by deleting Nron specifically in osteoclasts, tooth movement speed increased in Nron CKO mic e . These results indicate that lncRNAs could be potential targets to regulate osteoclastogenesis and orthodontic tooth movement speed in the clinic in the future.
研究领域:
分子生物学
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正畸学
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骨骼生物学
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产品关联
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2019
·
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
·
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
危险品化学品经营许可证（带存储）