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

Objective This study aims to demonstrate the cellular composition and underlying mechanisms in subchondral bone marrow lesions (BMLs) of knee osteoarthritis (OA). Methods BMLs were assessed by MRI Osteoarthritis Knee Score (MOAKS)≥2. Bulk RNA-sequencing (bulk-seq) and BML-specific differentially exp...

Celý popis

Uloženo v:
Podrobná bibliografie
Vydáno v:BMC musculoskeletal disorders Ročník 24; číslo 1; s. 1 - 14
Hlavní autoři: Zeng, Muhui, Wang, Xiaoshuai, Chen, Tianyu, Ruan, Guangfeng, Li, Jia, Xue, Song, Zhao, Yang, Hu, Zhiyang, Xie, Ye, Fan, Tianxiang, Chen, Shibo, Li, Yang, Wang, Qianyi, Zhang, Yue, Zhang, Rongkai, Lin, Lijun, Ding, Changhai, Zhu, Zhaohua
Médium: Journal Article
Jazyk:angličtina
Vydáno: London BioMed Central 25.08.2023
BioMed Central Ltd
Springer Nature B.V
BMC
Témata:
Algorithms
Analysis
Arthritis
Bone composition
Bone marrow
Bone marrow lesions
Care and treatment
Cartilage
Chondrocytes
Chromosome 5
Deconvolution algorithm
Development and progression
Encyclopedias
Epidemiology
Gene expression
Genetic aspects
Genomes
Health aspects
Interleukin 11
Internal Medicine
Knee
Lesions
Magnetic resonance imaging
Medicine
Medicine & Public Health
Microenvironments
MicroRNAs
Molecular modelling
Musculoskeletal diseases
Ontology
Orthopedics
Osteoarthritis
Rehabilitation
Rheumatology
RNA sequencing
Single-cell RNA sequencing
Sports Medicine
Subchondral bone
Transcriptomes
Transcriptomics
China
United States > US
Deconvolution algorithm
Subchondral bone
Single-cell RNA sequencing
Osteoarthritis
Bone marrow lesions
ISSN:1471-2474, 1471-2474
On-line přístup:Získat plný text
Tagy: Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
Popis
Shrnutí:Objective This study aims to demonstrate the cellular composition and underlying mechanisms in subchondral bone marrow lesions (BMLs) of knee osteoarthritis (OA). Methods BMLs 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. Results A 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. Conclusion IL11 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. Key points 1. IL11 and VCAN were identified as the core hub genes of BMLs in OA. 2. The “ has-miR-424-5p/lncRNA PVT1” and the “ 3,4-benzopyrene” were determined as crucial networks and ingredient targeting IL11 and VCAN , respectively. 3. The cluster of heterotopic-chondrocytes was determined abundant in BMLs by deconvoluting from scRNA-seq to bulk-seq, and positively correlated with the expression of hub genes.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
ISSN:1471-2474
1471-2474
DOI:10.1186/s12891-023-06676-4