Shenzhen Key Laboratory for Systems Medicine in Inflammatory Diseases, School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Sun Yat-sen University, Shenzhen, 518106, P. R. China.
Joint Centre of Translational Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, P. R. China.
Adv Sci (Weinh). 2023 May;10(15):e2204592. doi: 10.1002/advs.202204592. Epub 2023 Apr 5.
As major regulators on bone formation/resorption in response to mechanical stimuli, osteocytes have shown great promise for restoring bone injury. However, due to the unmanageable and unabiding cell functions in unloading or diseased environments, the efficacy of osteogenic induction by osteocytes has been enormously limited. Herein, a facile method of oscillating fluid flow (OFF) loading for cell culture is reported, which enables osteocytes to initiate only osteogenesis and not the osteolysis process. After OFF loading, multiple and sufficient soluble mediators are produced in osteocytes, and the collected osteocyte lysates invariably induce robust osteoblastic differentiation and proliferation while restraining osteoclast generation and activity under unloading or pathological conditions. Mechanistic studies confirm that elevated glycolysis and activation of the ERK1/2 and Wnt/β-catenin pathways are the major contributors to the initiation of osteoinduction functions induced by osteocytes. Moreover, an osteocyte lysate-based hydrogel is designed to establish a stockpile of "active osteocytes" to sustainably deliver bioactive proteins, resulting in accelerated healing through regulation of endogenous osteoblast/osteoclast homeostasis.
作为对机械刺激的骨形成/吸收的主要调节剂，骨细胞在骨损伤修复方面显示出巨大的应用潜力。然而，由于在卸载或患病环境中骨细胞的功能不可控且无法持续，骨细胞的成骨诱导效果受到了极大限制。在此，报道了一种简单的用于细胞培养的振荡液流（OFF）加载方法，该方法使骨细胞仅启动成骨过程而不会启动骨吸收过程。经过 OFF 加载后，骨细胞中会产生多种充足的可溶性介质，收集的骨细胞裂解物在卸载或病理条件下始终能强烈诱导成骨细胞分化和增殖，同时抑制破骨细胞生成和活性。机制研究证实，糖酵解的升高和 ERK1/2 和 Wnt/β-catenin 通路的激活是骨细胞诱导成骨诱导功能的主要原因。此外，设计了基于骨细胞裂解物的水凝胶以建立“活性骨细胞”的储存库，持续递送具有生物活性的蛋白质，通过调节内源性成骨细胞/破骨细胞的平衡来加速愈合。
