BIOCHEMICAL PHARMACOLOGY
·
2024
·
IF 5.3
Baixing Li,Yibin Hu,Yan Chen,Kexin Liu,Kewei Rong,Qi Hua,Shaotian Fu,Xiao Yang,Tangjun Zhou,Xiaofei Cheng,Kai Zhang,Jie Zhao
Intervertebral disc degeneration (IVDD) is a common degenerative disease which is closely related to low back pain (LBP) and brings huge economic and social burdens. In this study, we explored the therapeutic effects of Homoplantaginin (Hom) for IVDD due to its convincing anti-inflammatory and antioxidant functions. TNF-α was used to simulate the inflammatory environment for nucleus pulposus (NP) cells in vitro. We verified that Hom could alleviate the TNF-α-induced inflammation and disturbance of ECM homeostasis through blocking the NF-κB/MAPK signaling pathways. Subsequently, we screened the binding targets of Hom and confirmed that Hom could directly bind to TAK1 and inhibit its phosphorylation to down-regulate the inflammation-related pathways. The therapeutic effects of Hom on IVDD were further validated through a needle puncture rat model in vivo. Overall, Hom was a promising small molecule for IVDD early intervention, possessing huge clinical translational value.
研究领域:
药理学
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骨科
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
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2018
·Vol. 22
·期 11
·5720-5731
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IF 4.302
Jianle Wang,Chongan Huang,Zongze Lin,Xiangxiang Pan,Jiaoxiang Chen,Gang Zheng,Naifeng Tian,Yingzhao Yan,Zengjie Zhang,Jianing Hu,Pu Cheng,Xiangyang Wang,Xiaolei Zhang
Intervertebral disc degeneration (IVDD) is one of the major causes of low back pain. Polydatin (PD) has been shown to exert multiple pharmacological effects on different diseases; here, we test the therapeutic potential of PD for IVDD. In in-vitro experiments, we confirmed PD is nontoxic to nucleus pulposus cells (NPCs) under the concentration of 400 μmol/L. Furthermore, PD was able to decrease the level of senescence in TNF-α-treated NPCs, as indicated by β-gal staining as well as senescence markers p53 and p16 expression. In the aspect of extracellular matrix (ECM), PD not only reduced metalloproteinase 3 (MMP-3), metalloproteinase 13 (MMP-13) and a disintegrin-like and metalloproteinase thrombospondin type 1 motif 4 (ADAMTS-4) expression, but also increased aggrecan and collagen II levels. Mitochondrion is closely related to cellular senescence and ECM homeostasis; mechanistically, we found PD may rescue TNF-α-induced mitochondrial dysfunction, and it may also promote Nrf2 expression and activity. Silencing Nrf2 partly abolished the protective effects of PD on mitochondrial homeostasis, senescence and ECM homeostasis in TNF-α-treated NPCs. Correspondingly, PD ameliorated IVDD in rat model by promoting Nrf2 activity, preserving ECM and inhibiting senescence in nucleus pulposus cells. To sum up, our study suggests that PD exerts protective effects in NPCs against IVDD and reveals the underlying mechanism of PD on Nrf2 activation in NPCs.
研究领域:
药理学
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骨科
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2023
·
IF 19
Yanqiu Wang,Lu Tan,Wanqian Zhang,Yi Yang,Changqing Li,Hongli Li,Kaiyong Cai,Yan Hu,Zhong Luo,Minghan Liu
Intervertebral disc degeneration (IDD) remains an essential challenge in the clinics due to the ferroptosis of nucleus pulposus cells (NPCs) and the imbalance of extracellular matrix (ECM) metabolism. Here, a dynamic hydrogel (HPGO) based on oxidized hyaluronic acid (OHA) and polyvinyl alcohol (PVA) for the integration of oridonin (Ori)-loaded NPC membrane-based nanovesicles is proposed, which is further grafted with growth and differentiation factor 5 (GDF5) on the OHA chain via Schiff base ligation. The precursors can rapidly form mechanically resilience hydrogels after injection into nucleus pulposus (NP) through the formation of various dynamic bonds. Meanwhile, the acidic pH in the degenerated NP can trigger the responsive release of GDF5, which may cooperate with Ori to alleviate inflammation in the microenvironment for restoring the metabolic homeostasis of ECM. In addition, the Schiff base moieties in HPGO hydrogel can scavenge free ferrous ions in the microenvironment to strengthen the dynamic bonds for self-regulated reinforcement, thus providing mechanical support for the degenerated intervertebral discs (IVDs). Furthermore, HPGO hydrogel can enhance ferroptosis resistance of NPCs by activating the nuclear factor erythoid 2-related factor 2 signaling pathway. Overall, HPGO hydrogel can mechanically support the damaged IVDs as well as reversing their degenerative status through cooperative ferroptosis inhibition, which provides an approach for the clinical treatment of IDD.
研究领域:
生物医学工程
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组织工程
·
再生医学
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骨科
·
药学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）