Wan Wanting, Zhang Hui, Niu Lin, Zhang Min, Xu Feng, Li Ang, Pei Dandan, Lin Min, Cheng Bo
Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an 710004 P.R. China.
Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an 710049 P.R. China.
iScience. 2024 Jun 12;27(7):110262. doi: 10.1016/j.isci.2024.110262. eCollection 2024 Jul 19.
Positive autoregulation (PAR), one type of network motifs, provides a high phenotypic heterogeneity for cells to better adapt to their microenvironments. Typical mechanosensitive proteins can also form PAR, e.g., integrin mediated PAR, but the role of such mechanical PAR in physiological development and pathological process remains elusive. In this study, we found that transforming growth factor β1 (TGF-β1) and integrin levels decrease with tissue softening after the development of paradentium in rat model of periodontitis (an inflammatory disease with bone defect). Interestingly, TGF-β1 could induce the formation of mechanical PAR involving the integrin-FAK-YAP axis in mesenchymal stem cells (MSCs) by both experiments and computational model. The computational model predicted a mechanical PAR involving the bimodal distribution of focus adhesions, which enables cells to accurately perceive extracellular mechanical cues. Thus, our analysis of TGF-β1 mediated mechanosensing mechanism on MSCs may help to better understand the molecular process underlying bone regeneration.
正反馈自动调节（PAR）作为一种网络基序，为细胞提供了高度的表型异质性，使其能够更好地适应微环境。典型的机械敏感蛋白也可形成PAR，例如整合素介导的PAR，但这种机械性PAR在生理发育和病理过程中的作用仍不清楚。在本研究中，我们发现，在牙周炎大鼠模型（一种伴有骨缺损的炎症性疾病）的牙周组织发育后，随着组织软化，转化生长因子β1（TGF-β1）和整合素水平降低。有趣的是，通过实验和计算模型，TGF-β1均可在间充质干细胞（MSC）中诱导形成涉及整合素-FAK-YAP轴的机械性PAR。计算模型预测了一种涉及粘着斑双峰分布的机械性PAR，这使细胞能够准确感知细胞外机械信号。因此，我们对TGF-β1介导的MSC机械传感机制的分析可能有助于更好地理解骨再生的分子过程。
