PHYTOMEDICINE
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2023
·
IF 7.9
Shuai Chen,Jie Jin,Ziqing Xu,Huawei Han,Lan Wu,Zhiwei Li
Background Catalpol , a major active component of the Chinese herb Rehmannia glutinosa , possesses various pharmacological benefits, including anti-inflammatory, antidiabetic , and antitumor properties. Recent studies have reported that catalpol can attenuate bone loss and enhance bone formation. Nevertheless, the molecular mechanisms underlying its effects on osteoporosis pathogenesis remain unclear. Purpose We investigated whether catalpol had a protective effect against postmenopausal osteoporosis (PMOP) and explored its exact mechanism of action. Methods Seventy-two rats were randomly divided into six groups: sham, model, low-dose catalpol (5 mg/kg/day), medium-dose catalpol (10 mg/kg/day), high-dose catalpol (20 mg/kg/day), and positive control (alendronate, 2.5 mg/kg). In this experiment, a ovariectomy was performed to establish a female rat model of PMOP. After 12 weeks of gavage, micro-computed tomography (micro-CT) and histochemical staining were performed to evaluate bone mass, bone microstructure and histological parameters. Furthermore, RAW 264.7 cells were induced by RANKL to form mature osteoclasts to investigate the effect of catalpol on osteoclast differentiation and apoptosis in vitro . Additionally, the osteoclast apoptosis-related proteins of Sirt6 , ERα, FasL , NFATc1, cleaved-caspase 8, cleaved-caspase 3, and Bax were assessed using western blotting . The expressions of NFATc1, Ctsk, Oscar , and Trap were quantified using RT-qPCR. The apoptotic rate of the osteoclasts was determined using flow cytometry. Sirt6 knockdown was performed using siRNA gene silencing in experiments to investigate its role in catalpol-mediated osteoclast apoptosis. The deacetylation of ERα in osteoclasts was tested via co-immunoprecipitation. Results Catalpol (10 and 20 mg/kg) and alendronate (2.5 mg/kg) could significantly improve bone mineral density (BMD) and microstructure and decrease osteoclast density in ovariectomized (OVX) rats. In addition, catalpol (10 and 20 mg/kg) upregulated the expression of Sirt6, ERα, FasL, cleaved-caspase 8, cleaved-caspase 3, Bax, and downregulated the expression of NFATc1, Ctsk, Oscar, Trap both in vivo and in vitro . Catalpol also promoted ERα deacetylation and stabilized ERα protein to enhance the expression of FasL. In addition, Sirt6 knockdown by siRNA prevented ERα deacetylation and eliminated catalpol-mediated osteoclast apoptosis. Conclusions The present study demonstrated that catalpol prevents estrogen deficiency-induced osteoporosis by promoting osteoclast apoptosis via the Sirt6-ERα-FasL axis. These findings revealed a novel molecular mechanism underpinning the impact of catalpol in the progression of osteoporosis and provided novel insights into the treatment of osteoporosis.
研究领域:
药理学
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骨骼生物学
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分子生物学
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内分泌学
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DOI
PubMed
高影响因子
Materials Today Bio
·
2023
·
IF 8.2
Jiafeng Wang,Longhui Shao,Xiaoyu Wu,Chun Liu,Su Ni,Ting Dai,Hongwei Liu,Hongbin Zhao
Osteoblasts and osteoclasts play a crucial role in the dynamically coupled balance during bone regeneration and remodeling. They complement and restrict each other in the human body. Decreased osteoblasts lead to insufficient bone formation or excessive formation of osteoclasts, leading to increased bone resorption, which will destroy the structure of the bone tissue. This will greatly increase the risk of diseases such as osteoporosis and nonunions caused by bone defects. Herein, gelatin and polycaprolactone were used as substrates, and biomaterial membranes with mesh and sandwich structures were constructed using the electrospinning technology. Naringenin was loaded into the shell, and vitamin K 2 was loaded into the core layer of the nanofibrous membrane. The biocompatibility and osteogenic capacity of the membranes were assessed in vitro using mouse bone marrow mesenchymal stem cells (BMSCs). During osteoclast induction, the receptor activator of nuclear factor kappa-Β ligand (RANKL) was used to coculture RAW264.7 cells with various materials. The regulatory effect of various membranes on osteoclast growth was evaluated by detecting the expression levels of osteoclast-related genes and proteins in the cells. Subsequently, we constructed a model of a rat skull defect and implanted different membranes into the defect. Then, we evaluated the new bone formation in the defect using histological staining and micro-computed tomography after 4 and 8 weeks. The results of in vitro experiments confirmed that the incorporation of naringenin and vitamin K 2 stimulated the expression of osteogenesis-related genes and the secretion of osteogenesis-related proteins. Simultaneously, the results showed that naringenin and vitamin K 2 inhibited the formation and growth of osteoclasts. Therefore, naringenin and vitamin K 2 have a synergistic effect in promoting bone growth and regulating osteoclast growth.
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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细胞生物学
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL
·
2024
·
IF 1.5
Zheng Zhen,Fan Ying,Zhang Jingyun,Wang Jian,Li Zhenyu
Pharmacological studies have shown that Cedrol (CE) exhibits extensive biological activities, including anti-inflammatory and analgesic. Moreover, it can inhibit the NF-κB pathway and the expression of various associated proteins. This study aimed to investigate the role of CE in postmenopausal osteoporosis. The results showed that intragastric administration of CE (10 and 20 mg/kg) significantly improved the bone microstructure damage and increased bone mineral density, trabecular bone volume, and bone trabecular thickness in ovariectomized (OVX) rats ( p < 0.05). CE treatment additionally made a well-organized arrangement of bone trabeculae and improved its thickness and density. Compared with the OVX group, the levels of tartrate-resistant acid phosphatase from 5b and C-terminal telopeptide of type I collagen were significantly reduced by 42.75% and 49.27% in the OVX + CE rats ( p < 0.05). TRAP staining visually showed that the number of osteoclasts in the femur tissue of CE-treated rats was less than that of the OVX group. The expressions of nuclear factor of activated T-cells, cytoplasmic 1, acid phosphatase 5, and cathepsin K in OVX + CE rats were significantly decreased by 51.61%, 46.07%, and 50.34% compared to the OVX group ( p < 0.01). In addition, CE intervention effectively reduced the phosphorylation levels of P65 and IκBα and inhibited the NF-κB signaling pathway. Meanwhile, CE diminished the number of multinucleated osteoclasts induced by receptor activator for nuclear factor-κB ligand and hindered cell fusion as well as nuclear translocation of osteoclast precursor cells P65. In conclusion, CE inhibits osteoclastogenesis by suppressing the activation of the NF-κB signaling pathway, thereby alleviating postmenopausal osteoporosis.
研究领域:
药理学
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生物学
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医学
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内分泌学
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产品关联
DOI
PubMed
高影响因子
Food & Function
·
2023
·Vol. 14
·期 8
·3732-3745
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IF 6.1
Xinyan Liu,Ru Song,Rongbian Wei,Baoding Zhao,Yurou Chu
Vitamin D (VD) plays an important role in preventing osteoporosis. However, knowledge of the osteogenic effect of VD3 from shrimp processing by-products is limited. In this study, a VD3-rich extract from Penaeus sinensis processing by-products was prepared by saponification and liquid–liquid extraction combined with solid phase extraction for purification. The activity of purified VD3-rich extract (PPs-VD3) on MC3T3-E1, a preosteoblastic cell line, was determined. Furthermore, the improvement effect of PPs-VD3 on bone health of VD-deficient mice was investigated. PPs-VD3 stimulated the proliferation and differentiation of MC3T3-E1 cells. Compared to the same concentration of the VD3 standard, mineralization of MC3T3-E1 cells increased after 14 d or 21 d of PPs-VD3 treatment. Western blotting showed that PPs-VD3 significantly upregulated the protein levels of bone morphogenetic protein 2 and runt-related transcription factor 2 compared to the VD3 standard. Furthermore, PPs-VD3 treatment activated the receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin (OPG) signaling pathway in MC3T3-E1 cells, especially increased OPG expression was detected at day 3 to day 14 compared to the VD3 standard treatment. More than ten medium and long chain fatty acids were detected in PPs-VD3, of which n-3 polyunsaturated fatty acids (PUFA) constituted 38.83 ± 8.61%, and the n-3/n-6 PUFA ratio in PPs-VD3 was 2.84 ± 0.23. The femoral trabeculae number and thickness of VD-deficient mice increased after 3 weeks of PPs-VD3 treatment. The changes of parameters associated with bone resorption including parathyroid hormone, bone mineral density and tartrate resistant acid phosphatase revealed the contribution of PPs-VD3 treatment in improving bone remodeling in VD-deficient mice. Our results suggest that PPs-VD3 could have potential prospects in alleviating osteoporosis or promotion of bone health.
研究领域:
营养学
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药理学
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细胞生物学
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动物科学
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DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
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2022
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IF 6.1
Yanbei Tu,Lihua Tan,Tao Lu,Kai Wang,Haiyong Wang,Bing Han,Yuxin Zhao,Hanbin Chen,Yanfang Li,Haixia Chen,Meiwan Chen,Chengwei He
The roots of Glycine tabacina are used to treat rheumatoid arthritis (RA) and joint infection in folk medicine. Glytabastan B (GlyB), a newly reported coumestan isolated from this species, was found to significantly attenuate IL-1β-induced inflammation in SW982 human synovial cells at 3 and 6 μM, as evidenced by the decreased levels of pro-inflammatory mediators and matrix metalloproteinases (MMPs). GlyB also suppressed RANKL-induced osteoclastogenesis, decreased the expression of osteoclastogenic markers (NFATc1, CTSK , MMP-9) and osteoclast-mediated bone resorption. Further, GlyB administration (12.5 and 25 mg/kg) significantly inhibited inflammation, osteoclast formation and disease progression in collagen-induced arthritis (CIA) mice. Integration of network pharmacology , quantitative phosphoproteomic and experimental pharmacology results revealed that these beneficial actions were closely associated with the blockade of GlyB on the activation of MAPK , PI3K/AKT and their downstream signals including NF-κB and GSK3β/NFATc1. Drug affinity responsive target stability (DARTS) assay, cellular thermal shift (CETSA) assay and molecular docking analysis confirmed that there were direct interactions between GlyB and its target proteins ERK2 , JNK1 and class Ⅰ PI3K catalytic subunit p110 (α, β, δ and γ), which significantly contributed to the inhibition of activation of MAPK and PI3K/AKT pathways. In conclusion, these results strongly suggest GlyB is a promising multiple-target candidate for the development of agents for the prevention and treatment of RA.
研究领域:
药理学
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免疫学
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风湿病学
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生物化学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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