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Updated: Jan 10, 2026

Software-Assisted Quantitative Measurement of Osteoarthritic Subchondral Bone Thickness
Published on: March 18, 2022
Integrated analysis identifies conserved transcription factors TCF12, E2F1, and TEAD4 with diagnostic and therapeutic
Jingyang Cheng1, Rulong Cai1,2, Wei Lu3
1Department of Joint Surgery, Center for Orthopedic Surgery, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China.
Background:
Osteoarthritis (OA) is a multifactorial joint disease involving both cartilage and subchondral bone. The molecular mechanism of subchondral bone in OA is still unclear.
Objective:
This study aimed to identify key molecular targets and transcription factors (TFs) in subchondral bone that drive OA progression, with a focus on their diagnostic and therapeutic potential.
Methods:
Differentially expressed genes (DEGs) from human OA patients and rat OA models were analyzed using RNA-seq data from GEO database. Then functional enrichment analysis, including GSEA, GO and KEGG revealed high conservation. The iRegulon analysis was applied to identify common TFs. Bingo analysis linked TF target genes to OA-relevant biological functions, and single-cell RNA sequencing (sc-RNA seq) identified the primary cell types expressing these TFs. Finally, the expression of identified TFs was validated in human OA and animal OA samples using immunofluorescence (IF) and qPCR.
Results:
We identified 77 common DEGs in OA patients and rat models, including genes associated with bone development or remodeling. Functional enrichment analysis identified common biological processes, such as skeletal system development, and shared pathways, including calcium signaling, across both species. Moreover, iRegulon analysis identified three conserved TFs-Transcription Factor 12 (TCF12), E2F Transcription Factor 1 (E2F1), and TEA domain transcription factor 4 (TEAD4) in both humans and rats. Single-cell analysis revealed that TFs mainly originate from bone-related cell populations. Finally, experimental validation confirmed that TCF12 was up-regulated, while E2F1 and TEAD4 were down-regulated in human OA subchondral bone and mouse DMM model.
Conclusions:
This study highlights TCF12, E2F1, and TEAD4 as key regulators of subchondral bone remodeling in OA. Their conserved expression patterns across species and strong correlation with OA progression suggest their potential as novel diagnostic markers and therapeutic targets for OA intervention.
Insights
This study identifies three key transcription factors (TCF12, E2F1, TEAD4) involved in osteoarthritis (OA) subchondral bone remodeling. These factors show conserved expression across species and could serve as novel diagnostic markers and therapeutic targets for OA.
Area of Science:
- Genomics and Molecular Biology
- Orthopedics and Musculoskeletal Research
- Bioinformatics and Computational Biology
Background:
- Osteoarthritis (OA) is a complex joint disease affecting both cartilage and subchondral bone.
- The precise molecular mechanisms governing subchondral bone changes in OA remain largely undefined.
Purpose of the Study:
- To pinpoint critical molecular targets and transcription factors (TFs) within subchondral bone that influence OA progression.
- To evaluate the diagnostic and therapeutic potential of identified OA-related molecular targets.
Main Methods:
- RNA sequencing (RNA-seq) data from human OA patients and rat OA models were analyzed to identify differentially expressed genes (DEGs).
- Functional enrichment analyses (GSEA, GO, KEGG) and iRegulon analysis were employed to identify conserved TFs and their associated biological functions.
- Single-cell RNA sequencing (sc-RNA seq) and experimental validation (immunofluorescence, qPCR) were used to determine TF expression and cell-type specificity.
Main Results:
- 77 common DEGs were identified in human and rat OA samples, many linked to bone development and remodeling.
- Three conserved TFs—TCF12, E2F1, and TEAD4—were identified as key regulators in both species.
- TCF12 was upregulated, while E2F1 and TEAD4 were downregulated in OA subchondral bone, with expression primarily in bone-related cells.
Conclusions:
- TCF12, E2F1, and TEAD4 are highlighted as crucial regulators in OA subchondral bone remodeling.
- The conserved expression patterns and correlation with OA progression suggest these TFs are promising diagnostic markers and therapeutic targets for OA intervention.
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