Single-Cell RNA Sequencing Reveals Transcriptional Changes in the Cartilage of Subchondral Insufficiency Fracture of the Knee.
Single-Cell RNA Sequencing Reveals Transcriptional Changes in the Cartilage of Subchondral Insufficiency Fracture of the Knee.
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单细胞 RNA 测序揭示膝关节软骨下功能不全骨折软骨的转录变化
DOI：
10.2147/jir.s385648
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发表时间：
2022
影响因子：
4.5
通讯作者：
中科院分区：
文献类型：
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作者：
目的膝关节软骨下功能不全骨折（SIFK）是膝关节疼痛的常见原因，主要困扰老年人。到目前为止，软骨下骨的突然不全骨折如何影响SIFK和OA患者软骨的转录组学特征在很大程度上是未知的。方法采用单细胞RNA测序技术（scRNA-seq）鉴定SIFK和OA患者软骨中不同的细胞亚群，并评估转录组学差异。此外，通过组织学评价和免疫组织化学（IHC）染色证实了上述发现。结果发现SIFK患者软骨组织的转录组学特征与正常人和OA患者完全不同。因此，在SIFK软骨中鉴定了几种具有缺氧和软骨内骨化信号激活的新型细胞簇。软骨细胞轨迹分析和免疫组化染色显示，在SIFK发生过程中，包括TCF 4在内的转录因子表达上调，这可能驱动了软骨和纤维组织的反应性形成以及软骨内骨化的激活。结论本研究首次利用scRNA-seq技术阐明了SIFK和OA软骨中转录组的改变和不同的细胞类型亚群，为理解SIFK的发生和发展提供了新的视角。
Purpose Subchondral insufficiency fracture of the knee (SIFK) is a common cause of knee joint pain that mainly afflicts the elderly. Until now, how a sudden insufficiency fracture of subchondral bone affects the transcriptomic profiles of cartilage in SIFK and OA patients are largely unknown. Methods Single-cell RNA sequencing (scRNA-seq) was used to identify various cell subsets and evaluate transcriptomic differences in cartilage of SIFK and OA patients. In addition, the above findings were confirmed by histological evaluation and immunohistochemical (IHC) staining. Results We found that the transcriptomic profiles of cartilage in the SIFK patient was completely different from those of normal and OA patients. Accordingly, several novel cell clusters with activation of hypoxia and endochondral ossification signaling were identified in the SIFK cartilage. Chondrocyte trajectories analysis and IHC staining revealed that transcription factors including TCF4 were found to be highly up-regulated during the occurrence of SIFK, which might drive the reactive formation of cartilage and fibrous tissue and the activation of endochondral ossification. Conclusion This is the first report to elucidate the transcriptomic alterations and distinct cell type subpopulations in the cartilage of SIFK and OA by the use of scRNA-seq, which provides a new insight in the understanding of the initiation and progression of SIFK.