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.

Genes & Genomics
|November 26, 2025
PubMed
Abstract

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.

Related Concept Videos

Osteoclasts in Bone Remodeling01:31

Osteoclasts in Bone Remodeling

Osteoclasts are cells responsible for bone resorption and remodeling. They originate from hematopoietic progenitor cells present in the bone marrow. Numerous progenitor cells fuse to form multinucleated cells, each with 10-20 nuclei. A single osteoclast has a diameter of 150 to 200 µM. These cells have ruffled borders that break down the underlying bone tissue and release minerals such as calcium into the blood in bone resorption. Osteoclasts cling to bones with their ruffled edges during...
3.8K
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
7.7K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
10.4K
Bone Formation by Endochondral Ossification01:24

Bone Formation by Endochondral Ossification

Bone formation, or ossification, begins around the sixth to seventh week of embryonic development. Most bones develop from a cartilaginous template through the process of endochondral ossification. Cartilage formation begins when clusters of mesenchymal cells differentiate into chondrocytes. These chondrocytes proliferate rapidly and secrete an extracellular matrix that becomes encased in a membrane called the perichondrium. The resulting cartilage model provides a template that resembles the...
8.3K