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更新于：2025-11-24

CTSK x NFATC1

更新于：2025-11-24

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100 项与 CTSK x NFATC1 相关的转化医学

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0 项与 CTSK x NFATC1 相关的专利（医药）

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652

项与 CTSK x NFATC1 相关的文献（医药）

2026-02-01·JOURNAL OF ETHNOPHARMACOLOGY

Dioscorea polystachya Turcz. Extract attenuates osteoclastogenesis and ovariectomy-induced bone loss in rats

Article

作者: Lee, Donghun ; Lee, Juni ; Hwang, Ji Hye ; Kim, Surim ; Hwang, Yeseul ; Choi, Yeojin

ETHNOPHARMACOLOGICAL RELEVANCE:

Dioscorea polystachya Turcz. has been traditionally used in East Asian herbal medicine to strengthen bones and treat musculoskeletal conditions. However, the pharmacological mechanisms underlying its anti-osteoporotic effects remain poorly defined.

AIM OF THE STUDY:

This study aimed to investigate the anti-osteoporotic potential of D. polystachya root extract (DRE) through its effects on osteoclast differentiation and function, using both in vitro and in vivo models.

MATERIALS AND METHODS:

Osteoclastogenesis was induced in bone marrow-derived macrophages (BMMs) by stimulation with receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF), and the effects of DRE on osteoclast formation were assessed by tartrate-resistant acid phosphatase (TRAP) staining and qRT-PCR analysis of key osteoclastogenic genes (e.g., Nfatc1, c-Fos, Ctsk, Mmp9, Acp5). For in vivo analysis, ovariectomized (OVX) rats were orally administered DRE for eight weeks. Micro-computed tomography (micro-CT), histological staining (H&E and IHC for cathepsin K), and serum biomarker assays such as alkaline phosphatase (ALP) and TRAP were used to evaluate trabecular bone preservation and osteoclast activity.

RESULTS:

DRE significantly inhibited osteoclast formation and suppressed the expression of osteoclast-related transcription factors and functional markers in vitro. In OVX rats, DRE treatment dose-dependently attenuated trabecular bone loss, reduced serum ALP and TRAP levels, and preserved trabecular architecture. IHC analysis showed a marked reduction in cathepsin K-positive cells in the DRE-treated group compared to OVX controls.

CONCLUSIONS:

DRE exerts anti-osteoporotic effects by suppressing osteoclast differentiation and activity, thereby mitigating bone loss in estrogen-deficient conditions. These findings highlight the potential of D. polystachya as a promising natural therapeutic agent for the prevention and treatment of postmenopausal osteoporosis.

2026-01-01·JOURNAL OF ETHNOPHARMACOLOGY

Cervus elaphus sibiricus (deer antler) extract alleviates osteoporosis via dual modulation of osteoblast and osteoclast activity in ovariectomy-induced mice on network pharmacology

Article

作者: Park, Sung Hyo ; Jin, Seong Chul ; Choi, You Yeon ; Baek, Hee Kyung ; Park, Jieun ; Lee, Jin Young ; Yang, Hyun Jung ; Song, Minwoo ; Yang, Woong Mo ; Yi, Seungyob

ETHNOPHARMACOLOGICAL RELEVANCE:

Cervus elaphus sibiricus (deer antler; Cervi Parvum Cornu; Nokyong) refers to the unossified antlers of young male deer and has been traditionally used in East Asian medicine to tonify the kidney and strengthen bone, supporting musculoskeletal health (osteoporosis, age-related frailty). Despite its long-standing use, the pharmacological mechanisms underlying its anti-osteoporotic effects remain largely unelucidated.

AIM OF THE STUDY:

This study aimed to evaluate the anti-osteoporotic effects of a dual-extraction deer antler extract (PKDE) and to elucidate its mechanism of action through an integrative approach combining network pharmacology with in vivo and in vitro models.

MATERIALS AND METHODS:

Network pharmacology (KEGG, GO, PPI) was used to identify bone-related targets, and active compounds were verified by HPLC-MS. An ovariectomy (OVX)-induced osteoporosis mouse model was used to evaluate the in vivo efficacy of PKDE (48, 96, and 144 mg/kg, p.o., 4 weeks). Bone mineral density (BMD), bone mineral content (BMC), collagen deposition, and adipocyte size were assessed. Serum levels of TRACP-5b, CTX, and osteocalcin were measured. Osteogenic and osteoclastic gene expression in tibial tissue was analyzed by RT-PCR. In vitro, the effects of PKDE on osteoclastogenesis and osteoblast differentiation were investigated using RAW264.7 and SaOS-2 cells, respectively.

RESULTS:

PKDE increased BMD and BMC, restored collagen, and reduced marrow adiposity. Serum levels of TRACP-5b and CTX decreased, whereas osteocalcin increased. Gene expression analysis revealed downregulation of osteoclast markers (RANKL/OPG ratio) and upregulation of osteoblast markers (Col1a1, Bmp2, Spp1) in tibial tissue. In vitro, PKDE suppressed osteoclastogenesis in RANKL-induced RAW264.7 cells, as evidenced by a reduction in TRAP-positive multinucleated cells and downregulation of osteoclast-related genes such as Nfatc1 and Ctsk. In contrast, PKDE promoted osteoblast differentiation in AA/β-GP-induced SaOS-2 cells, as demonstrated by enhanced mineralization via Alizarin Red S staining and upregulated expression of osteogenic markers including COL1A1, BMP2, Runx2, SPP1, and IBSP. No hepatotoxicity or nephrotoxicity was observed.

CONCLUSION:

PKDE exerts dual anti-osteoporotic effects by inhibiting osteoclastogenesis and promoting osteoblast differentiation via modulation of bone metabolism pathways, supporting the traditional use of PKDE and highlighting its potential as a natural-origin therapeutic for bone health.

2025-12-31·ANNALS OF MEDICINE

Yougui pills prevent ovariectomy-induced bone loss by suppressing Th17 response and IL-17/NF-κB pathway

Article

作者: Lin, Luting ; Wang, Ningrui ; Zhang, Peng ; Wang, Ying ; Hu, Qimiao ; Miao, Yuqi ; Fei, Jun

BACKGROUND:

Osteoporosis is a chronic metabolic bone disease that causes excessive osteoclast formation, ultimately resulting in massive bone loss. Yougui pills (YGPs) are the classic traditional Chinese medicine formula with an anti-osteoporosis effect, but the underlying mechanisms are unknown.

MATERIALS AND METHODS:

The ameliorative impact of YGPs on bone loss in ovarectomized mice model was examined by Alcian Blue Haematoxylin (ABH) staining and micro-CT scanning. The "YGPs-osteoporosis-target" network was established and analyzed to explore the molecular mechanism of YGPs on osteoporosis. In addition, flow cytometry and immunohistochemistry (IHC) were used to detect the Th17 response and the expression levels of CD4, IL-17A, RANKL, and RORγt. Finally, we examined the expressions of p-P65, nuclear factor of activated T cells 1 (NFATc1), and cathepsin K (CTSK) by IHC and immunofluorescence (IF) staining to investigate the inhibitory effects of YGPs on osteoclast formation and function in vitro and in vivo.

RESULTS:

The results of ABH staining and micro-CT scanning showed that YGPs can significantly prevent bone loss. The 'YGPs-osteoporosis-target' network found that IL-17 is the key target, and its effects may be closely related to the upstream Th17 cells and the downstream NF-κB pathway of IL-17. Meanwhile, Th17 response and the expression levels of CD4, IL-17A, RANKL, and RORγt increased in the OVX group compared with the sham group, while YGPs treatment significantly reduced the above conditions. We also found that the number and function of osteoclasts (OCs) were significantly increased by incubation with IL-17, while YGPs treatment inhibited osteoclast formation and function. Furthermore, YGPs can suppress the expression of p-P65, NFATc1, and CTSK by IHC and IF staining in vitro and in vivo.

CONCLUSION:

YGPs can exert anti-osteoporosis effects by regulating osteoimmunity, and the mechanism is to inhibit osteoclast formation and bone loss by suppressing the Th17 response and IL-17/NF-κB pathway.

项与 CTSK x NFATC1 相关的新闻（医药）

2025-11-21

·生物谷

颞下颌关节痛有新解！ACS Nano｜不止止痛！干细胞外泌体直击“挂钩炎”根源，抑制破骨细胞，保住关节软骨

日常吃饭、说话时，颞下颌关节默默承担着咀嚼和运动的重任，可一旦患上颞下颌关节骨关节炎，疼痛、张口困难等问题便会严重影响生活质量。作为常见的退行性口腔疾病，颞下颌关节骨关节炎早期以软骨下骨过度丢失为特征，后期伴随软骨损伤，传统疗法如物理治疗、非甾体抗炎药等多只能缓解症状，难以阻止病变进展。近日，一项发表在ACS Nano的研究Mesenchymal Stem Cell-Derived Extracellular Vesicles Ameliorate Temporomandibular Joint Osteoarthritis by Suppressing Osteoclast Activity Via let-7a-5p/Integrin β3 Axis，为这一疾病的治疗带来了突破性新发现。研究团队首先对人脐带间充质干细胞（hUCMSC）及其来源外泌体（hUCMSC-EVs）进行了表征：hUCMSC呈梭形贴壁生长，高表达CD90、CD73、CD105等干细胞标志物，且具备成骨、成脂、成软骨的多向分化能力；通过超速离心法分离的hUCMSC-EVs，经透射电镜观察呈典型杯状或球形双层膜结构，纳米颗粒追踪分析显示其粒径峰值约126nm（主要分布于80-200nm），Western blot证实其表达CD63、Flot-1、CD81等外泌体特异性标志物，不表达内质网标志物Calnexin，且可被破骨细胞和巨噬细胞成功摄取。随后的体外实验证实hUCMSC-EVs可显著抑制破骨细胞分化：CCK-8实验表明不同浓度hUCMSC-EVs均具有良好生物相容性；在RANKL诱导破骨细胞分化体系中，加入hUCMSC-EVs后，第2、4、6天的TRAP活性均显著降低，第6天TRAP阳性多核破骨细胞数量明显减少且体积缩小；免疫荧光染色显示破骨细胞功能关键标志物CTSK的表达被显著抑制；RT-qPCR结果进一步证实，破骨细胞分化相关基因（CTSK、TRAP、NFATc1、CTR、DC-STAMP）的表达水平均显著下调。图1 人脐带间充质干细胞来源外泌体对破骨细胞分化的抑制作用为验证hUCMSC-EVs的体内治疗效果，研究团队构建了大鼠颞下颌关节骨关节炎模型（关节腔内注射单碘乙酸钠诱导），建模2周后每2周关节腔内注射hUCMSC-EVs（50μg）。体内荧光成像显示，注射的hUCMSC-EVs在颞下颌关节内可留存至第9天（第5天留存率22.56%，第9天11.75%）；μCT分析显示，对照组软骨下骨吸收明显（8周时更为显著），而hUCMSC-EVs处理组的骨体积/组织体积比值、骨小梁厚度显著升高，骨小梁分离度降低，软骨下骨结构更完整；组织学染色结果显示，hUCMSC-EVs组软骨结构保留更完好、蛋白多糖含量更高（番红O-固绿染色），TRAP阳性破骨细胞数量显著减少，OARSI软骨退变评分显著低于对照组，证实hUCMSC-EVs可同时保护颞下颌关节的软骨和软骨下骨。图2 人脐带间充质干细胞来源外泌体缓解颞下颌关节骨关节炎中的软骨下骨破坏进一步的机制研究揭示，hUCMSC-EVs通过传递let-7a-5p发挥作用：miRNA测序显示hUCMSC-EVs中富含134种共表达miRNA，Top20 miRNA的KEGG通路分析显示其富集于Wnt、MAPK等与破骨细胞分化相关的信号通路；其中let-7a-5p在RANKL诱导的破骨细胞中表达显著下调，而hUCMSC-EVs处理可恢复其表达水平；转染let-7a-5p模拟物后，破骨细胞的TRAP活性、阳性细胞数量及CTSK表达均显著降低，分化相关基因表达下调；通过TargetScan、miRDB、miRTarBase三大数据库预测并结合实验验证，证实let-7a-5p可直接靶向破骨细胞表面的Integrin β3（ITGβ3），双荧光素酶报告实验进一步确认let-7a-5p可结合ITGβ3的3'非翻译区，抑制其表达，进而抑制破骨细胞活性。图3 外泌体miRNA let-7a-5p抑制破骨细胞分化图4. 外泌体来源的let-7a-5p通过靶向Integrin β3抑制破骨细胞分化颞下颌关节骨关节炎的治疗长期受限于“治标难治本”，而这项发表在《ACS Nano》的研究，不仅明确了软骨下骨病变在疾病进展中的关键地位，更首次揭示了人脐带间充质干细胞外泌体通过let-7a-5p/Integrin β3轴调控破骨细胞活性的核心机制。未来随着转化研究的深入，有望让更多受颞下颌关节疼痛、功能受限困扰的患者摆脱疾病困扰，为口腔退行性疾病的治疗开辟全新路径。参考文献： Yang Z, Zhang S, Faqeer A, et al. Mesenchymal Stem Cell-Derived Extracellular Vesicles Ameliorate Temporomandibular Joint Osteoarthritis by Suppressing Osteoclast Activity Via let-7a-5p/Integrin β3 Axis. ACS Nano. Published online September 22, 2025. doi:10.1021/acsnano.5c11211 本文仅用于学术分享，转载请注明出处。若有侵权，请联系微信：bioonSir 删除或修改！点击下方「阅读原文」，前往生物谷官网查询更多生物相关资讯~

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