Wang Xinlong, Li Yiming, Lin Zitong, Pla Indira, Gajjela Raju, Mattamana Basil Baby, Joshi Maya, Liu Yugang, Wang Huifeng, Zun Amy B, Wang Hao, Wai Ching-Man, Agrawal Vasundhara, Dunton Cody L, Duan Chongwen, Jiang Bin, Backman Vadim, He Tong-Chuan, Reid Russell R, Luo Yuan, Ameer Guillermo A
Center for Advanced Regenerative Engineering, Northwestern University, Evanston, IL, USA.
Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA.
Nat Commun. 2025 Jul 11;16(1):6444. doi: 10.1038/s41467-025-60760-y.
Nuclear morphology plays a critical role in regulating gene expression and cell functions. While most research has focused on the direct effects of nuclear morphology on cell fate, its impact on the cell secretome and surrounding cells remains largely unexplored. In this study, we fabricate implants with a micropillar topography using methacrylated poly(octamethylene citrate)/hydroxyapatite (mPOC/HA) composites to investigate how micropillar-induced nuclear deformation influences cell secretome for osteogenesis and cranial bone regeneration. In vitro, cells with deformed nuclei show enhanced secretion of proteins that support extracellular matrix (ECM) organization, which promotes osteogenic differentiation in neighboring mesenchymal stromal cells (MSCs). In a female mouse model with critical-size cranial defects, nuclear-deformed MSCs on micropillar mPOC/HA implants elevate Col1a2 expression, contributing to bone matrix formation, and drive cell differentiation toward osteogenic progenitor cells. These findings indicate that micropillars modulate the secretome of hMSCs, thereby influencing the fate of surrounding cells through matricrine effects.
核形态在调节基因表达和细胞功能中起着关键作用。虽然大多数研究集中在核形态对细胞命运的直接影响上，但其对细胞分泌组和周围细胞的影响在很大程度上仍未被探索。在本研究中，我们使用甲基丙烯酸化聚（八亚甲基柠檬酸酯）/羟基磷灰石（mPOC/HA）复合材料制造具有微柱形貌的植入物，以研究微柱诱导的核变形如何影响细胞分泌组促进成骨和颅骨再生。在体外，核变形的细胞显示出支持细胞外基质（ECM）组织的蛋白质分泌增加，这促进了邻近间充质基质细胞（MSCs）的成骨分化。在具有临界尺寸颅骨缺损的雌性小鼠模型中，微柱mPOC/HA植入物上核变形的MSCs提高了Col1a2表达，有助于骨基质形成，并驱动细胞向成骨祖细胞分化。这些发现表明，微柱调节hMSCs的分泌组，从而通过基质分泌效应影响周围细胞的命运。
