Oscillating Fluid Flow Activated Osteocyte Lysate-Based Hydrogel for Regulating Osteoblast/Osteoclast Homeostasis to Enhance Bone Repair.
Oscillating Fluid Flow Activated Osteocyte Lysate-Based Hydrogel for Regulating Osteoblast/Osteoclast Homeostasis to Enhance Bone Repair.
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振荡液流激活的骨细胞裂解物基水凝胶用于调节成骨细胞/破骨细胞稳态以增强骨修复。
DOI：
10.1002/advs.202204592
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发表时间：
2023-05
期刊：
影响因子：
15.1
通讯作者：
Zhang, Xingding
中科院分区：
文献类型：
--
作者：
Zheng, Liyuan;Zhou, Disheng;Ju, Feier;Liu, Zixuan;Yan, Chenzhi;Dong, Zhaoxia;Chen, Shuna;Deng, Lizhi;Chan, Szehoi;Deng, Junjie;Zhang, Xingding
作为机械刺激下骨形成/吸收的主要调节因子，骨细胞在骨损伤修复中显示出巨大的潜力。然而，由于在卸载或病变环境中细胞功能的不可控和不持久，骨细胞诱导成骨的效果受到极大限制。本文报道了一种简单的振荡流体流动（OFF）加载细胞培养方法，该方法使骨细胞仅启动成骨而不启动骨溶解过程。OFF加载后，骨细胞中产生了多种充足的可溶性介质，收集到的骨细胞裂解物不可避免地诱导成骨细胞分化和增殖，同时在卸载或病理条件下抑制破骨细胞的产生和活性。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的骨诱导功能启动的主要因素。此外，一种基于骨细胞裂解液的水凝胶被设计用来建立“活性骨细胞”的储备，以可持续地递送生物活性蛋白，通过调节内源性成骨细胞/破骨细胞的稳态来加速愈合。本报告描述了一种由振荡流体流动（OFF）处理的骨细胞制备的基于骨细胞裂解液的新型水凝胶。它可以抵抗骨细胞的高动态特性和肿瘤细胞的攻击，诱导成骨细胞产生强大的成骨反应，并对破骨细胞分化有抑制作用。OFF处理的骨细胞可以通过控制ERK1/2和Wnt/β - catenin通路来操纵成骨/溶骨平衡。
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. This report describes a novel osteocyte lysate‐based hydrogel prepared from oscillating fluid flow (OFF)‐treated osteocytes. It can resist the effects of osteocytic highly dynamic properties and tumor cell attacks to induce a robust osteogenic response of osteoblasts and a suppressive effect on osteoclasts differetiation. The OFF‐treated osteocytes can manipulate osteogenesis/osteolysis balance through controlling the ERK1/2 and Wnt/β‐catenin pathways.
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