TNFAIP3 Derived from Skeletal Stem Cells Alleviated Rat Osteoarthritis by Inhibiting the Necroptosis of Subchondral Osteoblasts.

IF 4 2区 医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY STEM CELLS Pub Date : 2024-04-15 DOI:10.1093/stmcls/sxad097
Xiao-Tong Li, Zhi-Ling Li, Pei-Lin Li, Fei-Yan Wang, Xiao-Yu Zhang, Yu-Xing Wang, Zhi-Dong Zhao, Bo-Feng Yin, Rui-Cong Hao, Ning Mao, Wen-Rong Xia, Li Ding, Heng Zhu
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Abstract

Recent investigations have shown that the necroptosis of tissue cells in joints is important in the development of osteoarthritis (OA). This study aimed to investigate the potential effects of exogenous skeletal stem cells (SSCs) on the necroptosis of subchondral osteoblasts in OA. Human SSCs and subchondral osteoblasts isolated from human tibia plateaus were used for Western blotting, real-time PCR, RNA sequencing, gene editing, and necroptosis detection assays. In addition, the rat anterior cruciate ligament transection OA model was used to evaluate the effects of SSCs on osteoblast necroptosis in vivo. The micro-CT and pathological data showed that intra-articular injections of SSCs significantly improved the microarchitecture of subchondral trabecular bones in OA rats. Additionally, SSCs inhibited the necroptosis of subchondral osteoblasts in OA rats and necroptotic cell models. The results of bulk RNA sequencing of SSCs stimulated or not by tumor necrosis factor α suggested a correlation of SSCs-derived tumor necrosis factor α-induced protein 3 (TNFAIP3) and cell necroptosis. Furthermore, TNFAIP3-derived from SSCs contributed to the inhibition of the subchondral osteoblast necroptosis in vivo and in vitro. Moreover, the intra-articular injections of TNFAIP3-overexpressing SSCs further improved the subchondral trabecular bone remodeling of OA rats. Thus, we report that TNFAIP3 from SSCs contributed to the suppression of the subchondral osteoblast necroptosis, which suggests that necroptotic subchondral osteoblasts in joints may be possible targets to treat OA by stem cell therapy.

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骨骼干细胞提取的 TNFAIP3 可抑制软骨下成骨细胞的坏死,从而缓解大鼠骨关节炎。
最近的研究表明,关节中组织细胞的坏死在骨关节炎(OA)的发展过程中起着重要作用。本研究旨在探讨外源性骨骼干细胞(SSCs)对OA软骨下成骨细胞坏死的潜在影响。研究人员利用从人类胫骨平台分离的人类骨骼干细胞和软骨下成骨细胞进行了Western印迹、实时PCR、RNA测序、基因编辑和坏死检测。此外,还使用大鼠前交叉韧带横断OA模型来评估SSCs对体内成骨细胞坏死的影响。显微 CT 和病理数据显示,关节内注射 SSCs 能显著改善 OA 大鼠软骨下小梁骨的微结构。此外,SSCs 还能抑制 OA 大鼠软骨下成骨细胞和坏死细胞模型的坏死。对是否受到肿瘤坏死因子α刺激的 SSCs 进行大量 RNA 测序的结果表明,SSCs 衍生的肿瘤坏死因子α诱导蛋白 3(TNFAIP3)与细胞坏死相关。此外,来自 SSCs 的 TNFAIP3 在体内和体外都有助于抑制软骨下成骨细胞的坏死。此外,关节内注射过表达 TNFAIP3 的 SSCs 还能进一步改善 OA 大鼠软骨下小梁骨的重塑。因此,我们报告说,来自自体干细胞的TNFAIP3有助于抑制软骨下成骨细胞坏死,这表明关节中坏死的软骨下成骨细胞可能是干细胞疗法治疗OA的目标。
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来源期刊
STEM CELLS
STEM CELLS 医学-生物工程与应用微生物
CiteScore
10.30
自引率
1.90%
发文量
104
审稿时长
3 months
期刊介绍: STEM CELLS, a peer reviewed journal published monthly, provides a forum for prompt publication of original investigative papers and concise reviews. STEM CELLS is read and written by clinical and basic scientists whose expertise encompasses the rapidly expanding fields of stem and progenitor cell biology. STEM CELLS covers: Cancer Stem Cells, Embryonic Stem Cells/Induced Pluripotent Stem (iPS) Cells, Regenerative Medicine, Stem Cell Technology: Epigenetics, Genomics, Proteomics, and Metabonomics, Tissue-Specific Stem Cells, Translational and Clinical Research.
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