Pan Jun, Li Hanwen, Jin Kai, Jiang Huaye, Li Ke, Tang Yingchuang, Liu Zixiang, Zhang Kai, Chen Kangwu, Xu Zhuobin, Wang Huihui, Yang Huilin, Niu Junjie, Shi Qin, Chen Hao
Department of Orthopedics, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Key Laboratory of Animal Breeding Reproduction and Molecular Design for Jiangsu Province, College of Animal Science and Technology, Yangzhou University, Yangzhou, China.
Mater Today Bio. 2022 Dec 17;18:100519. doi: 10.1016/j.mtbio.2022.100519. eCollection 2023 Feb.
The periosteum on the skeletal surface creates a unique micro-environment for cortical bone homeostasis, but how this micro-environment is formed remains a mystery. In our study, we observed the cells in the periosteum presented elongated spindle-like morphology within the aligned collagen fibers, which is in accordance with the differentiated osteoblasts lining on the cortical surface. We planted the bone marrow stromal cells(BMSCs), the regular shaped progenitor cells, on collagen-coated aligned fibers, presenting similar cell morphology as observed in the natural periosteum. The aligned collagen topology induced the elongation of BMSCs, whichfacilitated the osteogenic process. Transcriptome analysis suggested the aligned collagen induced the regular shaped cells to present part of the periosteum derived stromal cells(PDSCs) characteristics by showing close correlation of the two cell populations. In addition, the elevated expression of PDSCs markers in the cells grown on the aligned collagen-coated fibers further indicated the function of periosteal topology in manipulating cells' behavior. Enrichment analysis revealed cell-extracellular matrix interaction was the major pathway initiating this process, which created an osteo-friendly micro-environment as well. At last, we found the aligned topology of collagen induced mechano-growth factor expression as the result of Igf1 alternative splicing, guiding the progenitor cells behavior and osteogenic process in the periosteum. This study uncovers the key role of the aligned topology of collagen in the periosteum and explains the mechanism in creating the periosteal micro-environment, which gives the inspiration for artificial periosteum design.
骨骼表面的骨膜为皮质骨稳态创造了独特的微环境，但这种微环境是如何形成的仍是一个谜。在我们的研究中，我们观察到骨膜中的细胞在排列的胶原纤维内呈现出细长的纺锤状形态，这与皮质表面排列的分化成骨细胞一致。我们将形状规则的祖细胞——骨髓基质细胞（BMSCs）接种在胶原包被的排列纤维上，其呈现出与天然骨膜中观察到的相似细胞形态。排列的胶原拓扑结构诱导BMSCs伸长，这促进了成骨过程。转录组分析表明，排列的胶原通过显示这两种细胞群体的密切相关性，诱导形状规则的细胞呈现出部分骨膜来源的基质细胞（PDSCs）特征。此外，在排列的胶原包被纤维上生长的细胞中PDSCs标志物的表达升高，进一步表明骨膜拓扑结构在操纵细胞行为方面的作用。富集分析揭示细胞-细胞外基质相互作用是启动这一过程的主要途径，这也创造了一个有利于成骨的微环境。最后，我们发现胶原的排列拓扑结构通过Igf1可变剪接诱导机械生长因子表达，引导祖细胞行为和骨膜中的成骨过程。这项研究揭示了骨膜中胶原排列拓扑结构的关键作用，并解释了创建骨膜微环境的机制，这为人工骨膜设计提供了灵感。
