Zeng Qiang, Zheng Huimin, Heng Boon Chin, Yao Weitong, Yang Yue, Jiang Shengjie, Deng Xuliang
Institute of Medical Technology, Peking University Health Science Center, Beijing, China.
Beijing Laboratory of Biomedical Materials, Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, China.
Front Bioeng Biotechnol. 2023 Jul 18;11:1217919. doi: 10.3389/fbioe.2023.1217919. eCollection 2023.
Chirality is a crucial mechanical cue within the extracellular matrix during tissue repair and regeneration. Despite its key roles in cell behavior and regeneration efficacy, our understanding of chirality-biased protein profile in vivo remains unclear. In this study, we characterized the proteomic profile of proteins extracted from bone defect areas implanted with left-handed and right-handed scaffold matrices during the early healing stage. We identified differentially-expressed proteins between the two groups and detected heterogenic characteristic signatures on day 3 and day 7 time points. Proteomic analysis showed that left-handed chirality could upregulate cell adhesion-related and GTPase-related proteins on day 3 and day 7. Besides, interaction analysis and in vitro verification results indicated that the left-handed chiral scaffold material activated Rho GTPase and Akt1, ultimately leading to M2 polarization of macrophages. In summary, our study thus improved understanding of the regenerative processes facilitated by chiral materials by characterizing the protein atlas in the context of bone defect repair and exploring the underlying molecular mechanisms of chirality-mediated polarization differences in macrophages.
手性是组织修复和再生过程中细胞外基质内的关键机械信号。尽管其在细胞行为和再生功效中起着关键作用，但我们对体内手性偏向蛋白质谱的了解仍不清楚。在本研究中，我们对早期愈合阶段植入左手性和右手性支架基质的骨缺损区域提取的蛋白质进行了蛋白质组学分析。我们鉴定了两组之间差异表达的蛋白质，并在第3天和第7天的时间点检测到异质性特征信号。蛋白质组学分析表明，左手性在第3天和第7天可上调细胞黏附相关蛋白和GTP酶相关蛋白。此外，相互作用分析和体外验证结果表明，左手性手性支架材料激活了Rho GTP酶和Akt1，最终导致巨噬细胞的M2极化。总之，我们的研究通过在骨缺损修复背景下表征蛋白质图谱并探索手性介导的巨噬细胞极化差异的潜在分子机制，从而增进了对手性材料促进再生过程的理解。
