Nutrients
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2022
·Vol. 14
·期 9
·1940
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IF 6.706
Kuaitian Wang,Xiao Kong,Mengdi Du,Wei Yu,Zhenhua Wang,Bo Xu,Jianrong Yang,Jingru Xu,Zhili Liu,Yongqiang Cheng,Jing Gan
DEDEQIPSHPPR, the calcium-binding peptide (CBP) identified in soy yogurt, was proven to be a potential cofactor in osteoporosis prevention in our previous study, but the mechanism was unknown. In this study, the activity of alkaline phosphatase (ALP) and osteocalcin (OCN), the regulation of RUNX2, and the expression of TβRI were investigated to elucidate the underlying mechanism. The results show that CBP upregulated ALP activity and OCN concentration and increased the expression of RUNX2 and the activation of the MAPK signaling pathway. Similarly, the expression of osteogenesis-related genes in osteoblasts also increased upon CBP treatment. Moreover, the CBP-induced enhancement of ALP activity and phosphorylation levels in the p38 pathway was inhibited by treatment with a p38 inhibitor (SB203538) and TβRI inhibitor (SB431542), respectively, suggesting that p38 and TβRI were involved in the osteogenic action. Based on the signaling pathways, the intracellular calcium concentration was significantly elevated by CBP, which was correlated with the increased behavioral functions and the relative fluorescence intensity of the bone mass. These findings suggest that CBP stimulates osteoblast differentiation and bone mineralization through the activation of RUNX2 via mechanisms related to the TβRI-p38-MAPK signaling pathways, further highlighting CBP’s important potential for treating osteoporosis.Keywords:bone remodeling;soy peptide CBP;osteoblast;differentiation;p38-MAPK;RUNX2
研究领域:
生物学
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生物化学
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药理学
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骨骼生物学
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DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
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2024
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IF 3.3
Yuhua Zuo,Chao Chen,Fasheng Liu,Hongmei Hu,Si Dong,Qinyuan Shen,Junquan Zeng,Ling Huang,Xinjun Liao,Zigang Cao,Zilin Zhong,Huiqiang Lu,Jianjun Chen
Background The global increase in the aging population has led to a higher incidence of osteoporosis among the elderly. Objective This study aimed to evaluate the protective properties of pinoresinol diglucoside (PDG), an active constituent of Eucommia ulmoides , against dexamethasone-induced osteoporosis and chondrodysplasia. Methods A zebrafish model of osteoporosis was established by exposing larval zebrafish to dexamethasone. The impact of PDG on bone mineralization was assessed through alizarin red and calcein staining. Alkaline phosphatase activity was quantified to evaluate osteoblast function. The influence of PDG on chondrogenesis was estimated using alcian blue staining. Fluorescence imaging and motor behavior analysis were employed to assess the protective effect of PDG on the structure and function of dexamethasone-induced skeletal teratogenesis. qPCR determined the expression of osteogenesis and Wnt signaling-related genes. Molecular docking was used to assess the potential interactions between PDG and Wnt receptors. Results PDG significantly increased bone mineralization and corrected spinal curvature and cartilage malformations in the zebrafish model. Furthermore, PDG enhanced swimming abilities compared to the model group. PDG mitigated dexamethasone-induced skeletal abnormalities in zebrafish by upregulating Wnt signaling, showing potential interaction with Wnt receptors FZD2 and FZD5. Conclusion PDG mitigates dexamethasone-induced osteoporosis and chondrodysplasia by promoting bone formation and activating Wnt signaling.
研究领域:
药理学
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生物学
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医学
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动物学
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分子生物学
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DOI
PubMed
高影响因子
Scientific Reports
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2025
·Vol. 15
·期 1
·1-13
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IF 3.9
Fan Xinyu,Zhang Ying,Li Xinyu,Ding Junhui,Huang Jiaolong,Lian Kai,Duan Peng,Hu Chunhui,Xu Junchang
In this study, the effects of Ginsenoside Rg1 (Rg1), the primary bioactive constituent of Panax ginseng roots, on glucocorticoid-induced osteoporosis (GIOP) were examined using a zebrafish model, with a focus on elucidating its underlying mechanisms. Our findings demonstrated that Rg1 treatment inhibited osteoporosis induced by methylprednisolone (PN), as evidenced by increased mineralisation area and integrated optical density in the spine and skull of zebrafish larvae. Rg1 reduced the expression of bglap (an osteogenic marker gene) and increased the expression of traf (an osteoclast marker gene) compared with the PN group. Behavioural analysis revealed that Rg1 alleviated PN-induced hypoactivity, resulting in enhanced motion speed. Furthermore, transcriptome analysis identified 383 genes reversed by Rg1 treatment, with significant enrichment in skeletal system development. KEGG analysis indicated that Rg1 influenced several signalling pathways primarily involved in retinol, fat, protein and lipid metabolism. Several genes related to skeletal system development and retinol metabolism were validated by qRT-PCR. In summary, this study provides scientific evidence for the potential mechanisms of Rg1 in the therapeutic intervention of GIOP, highlighting its promise as a potential pharmacological agent for the prevention and treatment of osteoporosis.
研究领域:
药理学
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分子生物学
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生物信息学
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内分泌学
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发育生物学
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代谢学
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DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
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2024
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IF 4.3
Xiaoyang Zhou,Kai Lian,Junjie Jia,Xue Zhao,Peng Duan,Jiaolong Huang,Yihua Shi
Epimedium is thought to enhance the integrity of tendons and bones, ease joint discomfort and rigidity and enhance kidney function. Although glucocorticoids are commonly used in clinical practice, the mechanism by which the active compound Epimedin C (EC) alleviates glucocorticoid‐induced osteoporosis (GIOP) is not well understood. The therapeutic potential of EC in treating GIOP was evaluated using alizarin red S staining, calcein immersion and fluorescence imaging, and bone mineralization, bone mass accumulation and bone density in zebrafish larvae were determined. Using the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, the key signalling pathways related to bone development were identified. A protein–protein interaction network (PPIN) was constructed to identify osteoclast characteristic genes and the findings were verified using real‐time quantitative PCR (RT‐qPCR). The bone tissue damage caused by prednisolone was reduced by EC. It also altered physiological processes, improved bone density, boosted mineralization and increased bone mass and activity. Subsequent empirical investigations showed that EC impacted the major signalling pathways involved in bone development, such as osteoclast differentiation, oestrogen, MAPK, insulin resistance, PPAR and AMPK signalling pathways. It also decreased the expression of genes typical of osteoclasts. The results of our study uncover a previously unknown function of EC in controlling bone formation and emphasize the potential of EC as a therapeutic target. The osteoprotective effect of EC indicates its potential as a cost‐effective strategy for treating GIOP.
研究领域:
药理学
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生物学
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基因组学
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分子生物学
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生物信息学
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2022
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IF 10.383
Kaiyu Liang,Chenchen Zhao,Chenxin Song,Lan Zhao,Pengcheng Qiu,Shengyu Wang,Jinjin Zhu,Zhe Gong,Zhaoming Liu,Ruikang Tang,Xiangqian Fang,Yueqi Zhao
A critical-sized bone defect, which cannot be repaired through self-healing, is a major challenge in clinical therapeutics. The combination of biomimetic hydrogels and nano-hydroxyapatite (nano-HAP) is a promising way to solve this problem by constructing an osteogenic microenvironment. However, it is challenging to generate nano-HAP with a similar morphology and structure to that of natural bone, which limits the improvement of bone regeneration hydrogels. Inspired by our previous works on organic–inorganic cocross-linking, here, we built a strong organic–inorganic interaction by cross-linking periosteum-decellularized extracellular matrix and calcium phosphate oligomers, which ensured the in situ mineralization of bone-like nano-HAP in hydrogels. The resulting biomimetic osteogenic hydrogel (BOH) promotes bone mineralization, construction of immune microenvironment, and angiogenesis improvement in vitro. The BOH exhibited acceleration of osteogenesis in vivo, achieving large-sized bone defect regeneration and remodeling within 8 weeks, which is superior to many previously reported hydrogels. This study demonstrates the important role of bone-like nano-HAP in osteogenesis, which deepens the understanding of the design of biomaterials for hard tissue repair. The in situ mineralization of bone-like nano-HAP emphasizes the advantages of inorganic ionic oligomers in the construction of organic–inorganic interaction, which provides an alternative method for the preparation of advanced biomimetic materials.
研究领域:
组织工程
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生物材料
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骨再生
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生物医学工程
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2021
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IF 13.273
Lu Tan,Yan Hu,Menghuan Li,Yuchen Zhang,Chencheng Xue,Maohua Chen,Zhong Luo,Kaiyong Cai
The biomineralization of calcium ions and phosphate ions in the extracellular matrix (ECM) is a key event in bone regeneration, and it’s of therapeutic significance to develop biomaterials capable of mimicking the physiological biomineralization process, which is especially desirable in cranial defect repairing. For this purpose, we design a composite remotely-activatable ECM-mimetic chitosan/collagen-based hydrogel incorporated with mesenchymal stem cell (MSC)-membrane-coated black phosphorus (BP), which is a photothermal material with versatile utility. Here, the MSC membrane-coated BP nanosheets could induce mild photothermal effect under near-infrared (NIR) light to stimulate the osteoblast recruitment via activating the heat shock proteins (HSPs)-mediated matrix metalloproteinase (MMP) and ERK-Wnt/β-catenin-RUNX2 axis. Meanwhile, the thermal decomposition of BP would release phosphate ions into the surrounding medium to attract calcium ions to form hydroxyapatite in the ECM in an in-situ manner, which is beneficial for osteoblast migration and osteogenic differentiation. After the implantation in to the cranial defect site on Sprague Dawley (SD) rats, it was evidently observed that the hydrogel treatment substantially enhanced the local bone density and promoted new bone formation. Overall, the ECM-mimetic BP-incorporated hydrogel could enhance osteoblast migration/differentiation and stimulate the biomineralization process under remote NIR activation to promote bone healing, which offers new opportunities for repairing cranial defect in the clinics.
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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光热疗法
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生物医学工程
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产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
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2022
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IF 10.383
Baoshuai Bai,Junxiang Hao,Mengjie Hou,Tao Wang,Xiaodi Wu,Yanhan Liu,Yiyang Wang,Chengxiang Dai,Yujie Hua,Guangyu Ji,Guangdong Zhou
Tissue engineering technology provides a promising approach for large-scale bone reconstruction in cases of extensive chest wall defects. However, previous studies did not consider meticulous scaffold design specific to large-scale rib regeneration in terms of three-dimensional (3D) shape, proper porous structures, enough mechanical strength, and osteogenic microenvironments. Thus, there is an urgent need to develop an appropriate bone biomimetic scaffold (BBS) to address this problem. In this study, a BBS with controllable 3D morphology, appropriate mechanical properties, good biocompatibility and biodegradability, porous structure suitable for cell loading, and a biomimetic osteogenic inorganic salt (OIS) microenvironment was successfully prepared by integrating computer-aided design, 3D-printing, cast-molding, and freeze-drying technologies. The addition of the OIS in the scaffold substantially promoted ectopic bone regeneration in vivo, which might be attributed to the activation of osteogenic and angiogenic signaling pathways as well as upregulated expression of osteogenic genes. More importantly, dual long rib defects could be successfully repaired and medullary cavity recanalized by the rib-shaped mature cortical bone, which might be mediated by the activation of osteoclast signaling pathways. Thus, this paper presents a reliable BBS and proposes a new strategy for the repair of large-scale bone defects.
研究领域:
组织工程
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生物医学工程
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材料科学
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再生医学
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DOI
PubMed
高影响因子
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