Comprehensive analysis on subchondral bone marrow lesions of human osteoarthritis by integrating bulk and single-cell transcriptomes

BMC Musculoskeletal Disorders

Research

Guangfeng Ruan¹  Yang Zhao²  Tianxiang Fan²  Qianyi Wang²  Yang Li²  Shibo Chen²  Muhui Zeng³  Xiaoshuai Wang⁴  Jia Li⁴  Zhaohua Zhu⁴  Changhai Ding⁵  Rongkai Zhang⁶  Tianyu Chen⁶  Lijun Lin⁷  Song Xue⁸  Yue Zhang⁹  Zhiyang Hu^1,10  Ye Xie^1,11 

[1] Clinical Research Centre, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, China;Clinical Research Centre, Zhujiang Hospital, Southern Medical University, 510280, Guangzhou, Guangdong, China;Clinical Research Centre, Zhujiang Hospital, Southern Medical University, 510280, Guangzhou, Guangdong, China;Department of Orthopedics, General Hospital of Southern Theater Command of PLA, Guangzhou, Guangdong, China;Clinical Research Centre, Zhujiang Hospital, Southern Medical University, 510280, Guangzhou, Guangdong, China;Department of Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China;Clinical Research Centre, Zhujiang Hospital, Southern Medical University, 510280, Guangzhou, Guangdong, China;Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia;Department of Orthopedics, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China;Department of Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China;Department of Rheumatology and Immunology, Arthritis Research Institute, The First Affiliated Hospital of Anhui Medical University, Hefei, China;State Key Laboratory of Organ Failure Research, Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China;Sun Yat-sen University School of Medicine, Sun Yat-sen University, Shenzhen, China;Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China;

关键词: Osteoarthritis;    Subchondral bone;    Bone marrow lesions;    Deconvolution algorithm;    Single-cell RNA sequencing;   

DOI  :  10.1186/s12891-023-06676-4

 received in 2022-08-31, accepted in 2023-06-29,  发布年份 2023

来源: Springer

【 摘 要 】

ObjectiveThis study aims to demonstrate the cellular composition and underlying mechanisms in subchondral bone marrow lesions (BMLs) of knee osteoarthritis (OA).MethodsBMLs were assessed by MRI Osteoarthritis Knee Score (MOAKS)≥2. Bulk RNA-sequencing (bulk-seq) and BML-specific differentially expressed genes (DEGs) analysis were performed among subchondral bone samples (including OA-BML=3, paired OA-NBML=3; non-OA=3). The hub genes of BMLs were identified by verifying in independent datasets and multiple bioinformatic analyses. To further estimate cell-type composition of subchondral bone, we utilized two newly developed deconvolution algorithms (MuSiC, MCP-counter) in transcriptomic datasets, based on signatures from open-accessed single-cell RNA sequencing (scRNA-seq). Finally, competing endogenous RNA (ceRNA) and transcription factor (TF) networks were constructed through multiple predictive databases, and validated by public non-coding RNA profiles.ResultsA total of 86 BML-specific DEGs (up 79, down 7) were identified. IL11 and VCAN were identified as core hub genes. The “has-miR-424-5p/lncRNA PVT1” was determined as crucial network, targeting IL11 and VCAN, respectively. More importantly, two deconvolution algorithms produced approximate estimations of cell-type composition, and the cluster of heterotopic-chondrocyte was discovered abundant in BMLs, and positively correlated with the expression of hub genes.ConclusionIL11 and VCAN were identified as the core hub genes of BMLs, and their molecular networks were determined as well. We profiled the characteristics of subchondral bone at single-cell level and determined that the heterotopic-chondrocyte was abundant in BMLs and was closely linked to IL11 and VCAN. Our study may provide new insights into the microenvironment and pathological molecular mechanism of BMLs, and could lead to novel therapeutic strategies.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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