黄精多糖通过S100A9抑制介导的自噬促进调节软骨细胞炎症和代谢,改善骨关节炎

Polygonatum sibiricum polysaccharides regulate chondrocyte inflammation and metabolism via S100A9 inhibition-mediated autophagy promotion to ameliorate osteoarthritis.

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摘要(中文译文)

黄精(Polygonatum sibiricum,P. sibiricum)多糖(PSP)是药食两用植物黄精根中的主要生物活性成分,已被证明具有强烈的抗炎活性。然而,PSP在缓解骨关节炎(OA)相关软骨退变中的作用及其潜在机制——尤其是其与自噬的关联——仍不明确。本研究旨在探讨PSP如何影响软骨和软骨细胞中的自噬,并阐明所涉及的机制。采用高效凝胶渗透色谱法(HPGPC)测定PSP的分子量,并使用1-苯基-3-甲基-5-吡唑啉酮(PMP)-HPLC分析单糖组成。通过使用慢病毒载体进行基因过表达,构建了过表达p65/S100钙结合蛋白A9(S100A9)的软骨细胞。通过透射电子显微镜检测软骨细胞自噬体,并通过WB、免疫荧光和ELISA鉴定软骨细胞相关蛋白的表达水平。在体内实验中,通过部分内侧半月板切除术建立C57BL/6小鼠OA模型。将过表达慢病毒注射到关节腔并转染至关节软骨,构建S100A9过表达模型。结果表明,PSP可通过增强软骨细胞自噬改善白细胞介素-1β(IL-1β)诱导的软骨细胞外基质代谢紊乱和炎症反应,从而恢复IL-1β诱导的自噬损伤。RNA-seq分析显示,PSP抑制了IL-1β诱导的软骨细胞中S100A9的表达。进一步的机制证据表明,PSP通过S100A9/核因子κB(NF-κB)信号通路促进软骨细胞自噬,从而减轻软骨细胞炎症和基质代谢紊乱。体内和体外证据均支持PSP通过抑制S100A9/NF-κB通路促进软骨细胞自噬,从而达到改善OA的效果。这一发现凸显了PSP作为治疗OA的有价值天然植物来源化合物的潜力。

Abstract

Polygonatum sibiricum (P. sibiricum) polysaccharides (PSP), the main bioactive component in the roots of the medicinal and edible plant P. sibiricum, have been shown to exhibit strong anti-inflammatory activity. However, the role of PSP in alleviating osteoarthritis (OA)-related cartilage degeneration and the underlying mechanism-particularly its association with autophagy-remain elusive. This study aimed to investigate how PSP influences autophagy in the cartilage and chondrocytes, and to clarify the mechanisms involved. The molecular weight of PSP was measured using high-performance gel permeation chromatography (HPGPC), and the monosaccharide composition was analyzed using 1-phenyl-3-methyl-5-pyrazolone (PMP)-HPLC. Chondrocytes overexpressing p65/ S100 calcium-binding protein A9 (S100A9) were generated through the use of lentiviral vectors for gene overexpression. Autophagosomes of chondrocytes were detected by transmission electron microscope, and the expression levels of proteins associated with chondrocytes was identified through WB, immunofluorescence and ELISA. In vivo, the C57BL/6 mice model of OA was created by means of partial medial meniscectomy. Overexpressed lentivirus was injected into the joint cavity and transfected to articular cartilage, constructing an S100A9 overexpression model. The results demonstrated that PSP can ameliorate interleukin-1β (IL-1β)-induced metabolic dysregulation and inflammatory responses in the chondrocyte extracellular matrix by enhancing chondrocyte autophagy, thereby restoring the impaired autophagy induced by IL-1β. RNA-seq analysis revealed that PSP inhibited the expression of S100A9 in IL-1β-induced chondrocytes. Further mechanistic evidence indicated that PSP promoted chondrocyte autophagy via the S100A9/nuclear factor κB (NF-κB) signaling pathway, thus alleviating chondrocyte inflammation and matrix metabolic disorders. Both in vivo and in vitro evidence supports that PSP promotes chondrocyte autophagy by suppressing the S100A9/NF-κB pathway to achieve the outcome of OA improvement. This discovery highlights the potential of PSP as a valuable natural plant-derived compound in OA treatment.

如何引用

AMA

Shida Kuang, Qiyou Ding, Li Lin, Linhu Li, Zhewen Liu, Qinghu He, et al. Polygonatum sibiricum polysaccharides regulate chondrocyte inflammation and metabolism via S100A9 inhibition-mediated autophagy promotion to ameliorate osteoarthritis.. BMC complementary medicine and therapies. 2026; doi:10.1186/s12906-026-05467-3.

APA

Shida Kuang, Qiyou Ding, Li Lin, Linhu Li, Zhewen Liu, Qinghu He, et al (2026). Polygonatum sibiricum polysaccharides regulate chondrocyte inflammation and metabolism via S100A9 inhibition-mediated autophagy promotion to ameliorate osteoarthritis.. BMC complementary medicine and therapies. https://doi.org/10.1186/s12906-026-05467-3

GB/T 7714

Shida Kuang, Qiyou Ding, Li Lin, Linhu Li, Zhewen Liu, Qinghu He, et al. Polygonatum sibiricum polysaccharides regulate chondrocyte inflammation and metabolism via S100A9 inhibition-mediated autophagy promotion to ameliorate osteoarthritis.[J]. BMC complementary medicine and therapies, 2026 doi:10.1186/s12906-026-05467-3.

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