Machireddy Meghana, Nano Sarah, Debiase Lucas, Lewis Jonathan, Cole Sara, Li Jun, Niebur Glen L
University of Notre Dame, Bioengineering Graduate Program, Notre Dame, IN, USA.
Department of Aerospace and Mechanical Engineering, Notre Dame, IN, USA.
Sci Rep. 2025 May 27;15(1):18501. doi: 10.1038/s41598-025-00214-z.
Osteocytes regulate the response of osteoclasts and osteoblasts to mechanical loading through signaling molecules, the levels of which are controlled by post-translational modification or degradation and by differential gene transcription and translation. The magnitude and mode of bone tissue deformation that elicits a transcriptional response in individual osteocytes in situ has been difficult to quantify. We measured SOST, Wnt11, TNF, and FRZB gene expression in osteocytes within loaded and unloaded control porcine trabecular bone explants using RNAScope® and compared the local tissue level strain and strain gradient-which we used as an indicator of potential poroelastic fluid flow-in the tissue surrounding osteocytes with high vs. low gene expression. The measured expression of all four genes differed between loaded and unloaded explants, on average, with the mean SOST expression level decreasing by 45%. In the loaded explants, gene expression was altered from baseline in about 30% of the osteocytes, and they were surrounded by tissue with higher strain and strain gradient than the 20 to 25% of osteocytes that remained near baseline expression. Both deviatoric strain and hydrostatic strain gradient were sensitive and specific predictors of the mechanobiological response for individual genes as well as combinations. SOST expression was highly related to elevated strain gradient, providing evidence that osteocytes respond to fluid flow in the lacunar-canalicular system.
骨细胞通过信号分子调节破骨细胞和成骨细胞对机械负荷的反应，这些信号分子的水平由翻译后修饰或降解以及差异基因转录和翻译控制。在原位单个骨细胞中引发转录反应的骨组织变形的大小和模式一直难以量化。我们使用RNAScope®测量了加载和未加载的对照猪小梁骨外植体中骨细胞的SOST、Wnt11、TNF和FRZB基因表达，并比较了局部组织水平应变和应变梯度（我们将其用作潜在孔隙弹性流体流动的指标）在基因表达高与低的骨细胞周围组织中的情况。平均而言，加载和未加载的外植体中所有四个基因的测量表达均存在差异，SOST平均表达水平下降了45%。在加载的外植体中，约30%的骨细胞基因表达从基线改变，它们周围组织的应变和应变梯度高于仍接近基线表达的20%至25%的骨细胞。偏应变和静水应变梯度都是单个基因以及基因组合的力学生物学反应的敏感和特异性预测指标。SOST表达与升高的应变梯度高度相关，这证明骨细胞对腔隙-小管系统中的流体流动有反应。
