Osteocyte TGFβ1-Smad2/3 is positively associated with bone turnover parameters in subchondral bone of advanced osteoarthritis
Osteocyte TGFβ1-Smad2/3 is positively associated with bone turnover parameters in subchondral bone of advanced osteoarthritis
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DOI：
10.3892/ijmm.2020.4576
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发表时间：
2020-07-01
影响因子：
5.4
通讯作者：
Huang, Wei
中科院分区：
文献类型：
--
作者：
Dai, Guangming;Xiao, Haozhuo;Huang, Wei
软骨下硬化被认为是晚期骨关节炎的主要特征，其中转化生长因子β（TGFβ）信号介导的骨重塑在代谢中起着不可或缺的作用。由于其机械感应和内分泌功能，骨细胞已被确定为骨代谢的关键调节因子。因此，本研究的目的是探讨骨细胞TGFβ信号与软骨下硬化之间的关联。从骨关节炎患者身上采集膝关节胫骨平台样本，并将其分为三组：全软骨组、部分软骨组和完全缺损组。接下来，检测了骨细胞 TGF β 信号传导和各种类型软骨侵蚀背后的软骨下骨结构的变化。骨密度（BMD）测定、组织学[苏木精和伊红、番红-O/固绿和抗酒石酸酸性磷酸酶（TRAP）染色]和逆转录定量PCR主要检测软骨和软骨下骨的结构改变、成骨和破骨活性。通过免疫组织化学和蛋白质印迹检测软骨下骨中TGFβ信号通路的激活。通过相关性分析分析骨细胞TGFβ与骨代谢调节之间的关系，并在体外得到进一步证明。证实部分软骨组和完全缺损组软骨下骨的BMD增加并发生硬化。其他观察结果包括钙化软骨区域变薄，局部形成骨岛，软骨下骨板增厚，骨小梁体积增加。 TRAP染色表明部分软骨和完全缺损组的软骨下底层区域的骨吸收增加。免疫组织化学结果证实了软骨严重侵蚀的软骨下区域中骨细胞 TGF β 的激活。此外，骨细胞磷酸化-Smad2/3与软骨下BMD、碱性磷酸酶、骨桥蛋白mRNA表达量呈正相关，与TRAP(+)细胞呈负相关。此外，体外证实骨细胞TGFβ信号传导可以调节间充质干细胞的成骨和破骨活性。本研究表明骨细胞TGFβ信号与晚期骨关节炎软骨下骨的重塑呈正相关，为进一步研究骨细胞TGFβ在骨关节炎软骨下的作用和机制提供了初步的理论基础。
Subchondral sclerosis is considered the main characteristic of advanced osteoarthritis, in which bone remodeling mediated by transforming growth factor beta (TGF beta) signaling plays an indispensable role in the metabolism. Osteocytes have been identified as pivotal regulators of bone metabolism, due to their mechanosensing and endocrine function. Therefore, the aim of the present study was to investigate the association between osteocyte TGF beta signal and subchondral sclerosis. Knee tibia plateau samples were collected from osteoarthritic patients and divided into three groups: The full cartilage, partial cartilage and full defect groups. Next, changes in osteocyte TGF beta signaling and subchondral bone structure underlying various types of cartilage erosion were detected. Bone mineral density (BMD) assay, histology [hematoxylin and eosin, Safranin-O/Fast green, and tartrate resistant acid phosphatase (TRAP) staining], and reverse transcription-quantitative PCR mainly detected structural alterations, osteogenic and osteo-clastic activity in the cartilage and subchondral bone. The activation of the TGF beta signaling pathway in the subchondral bone was detected by immunohistochemistry and western blotting. The association between osteocyte TGF beta and the regulation of bone metabolism was analyzed by correlation analysis, and further proven in vitro. It was confirmed that the BMD of the subchondral bone increased and underwent sclerosis in the partial cartilage and full defect groups. Additional observation included the thinning of the area of calcified cartilage, in which a bone island formed locally, with subchondral bone plate thickening and increased trabecular bone volume. TRAP staining suggested an increase in bone resorption in subchondral underlying areas of the partial cartilage and full defect groups. Immunohistochemistry results confirmed the activation of osteocyte TGF beta in subchondral underlying areas with severe cartilage erosion. Moreover, osteocyte phosphorylated-Smad2/3 was positively correlated with subchondral BMD, alkaline phosphatase and osteopontin mRNA expression, but it was negatively correlated with TRAP(+) cells. Furthermore, it was confirmed in vitro that osteocyte TGF beta signaling could regulate the osteogenic and osteoclastic activity of the mesenchymal stem cells. This study illustrated that osteocyte TGF beta signaling is positively associated with the remodeling of subchondral bone in advanced osteoarthritis and provides a preliminary theoretical basis for further investigations of the role and mechanism of osteocyte TGF beta in subchondral of osteoarthritis.