# DEC1 regulates osteoblast proliferation and differentiation via the RUNX2 signaling pathway: Insights into the molecular mechanism of DEC1-mediated transcriptional regulation in bone metabolism

## TL;DR

This study explores how DEC1 influences bone metabolism by regulating the RUNX2 signaling pathway, affecting both osteoblast and osteoclast activity.

## Contribution

The study reveals a novel regulatory mechanism of DEC1 in bone metabolism through its interaction with the RUNX2 signaling pathway.

## Key findings

- DEC1 knockout mice showed reduced bone mineral density and structural parameters under ovariectomy conditions.
- DEC1 knockdown increased RUNX2 expression but impaired osteoblast differentiation in vitro.
- ChIP-seq confirmed RUNX2 enrichment near gene transcription start sites, linking DEC1 to RUNX2 activity.

## Abstract

Differentiated embryo chondrocyte 1 (Dec1, protein DEC1) plays a critical role in bone metabolism, but its interaction with the Runt-related transcription factor 2 (RUNX2) signaling pathway remains poorly understood. To investigate how DEC1 regulates osteoblast and osteoclast differentiation through the RUNX2 signaling pathway. To model estrogen deficiency–induced osteoporosis, ovariectomy (OVX) was performed in DEC1 knockout (DEC1−/−) and wild-type (DEC1+/+) mice, and bone parameters were assessed by micro-computed tomography (micro-CT). Primary bone marrow mesenchymal stem cells (BMSCs) were isolated for osteoblast induction, and RAW 264.7 macrophage-like cells were used for osteoclast differentiation. Flow cytometry was applied to assess lineage markers. RUNX2 expression and transcriptional activity were analyzed by qRT-PCR, Western blotting, GFP-tagging, and chromatin immunoprecipitation sequencing (ChIP-seq). DEC1−/− mice showed significant reductions in bone mineral density (BMD), bone volume fraction (BV/TV), trabecular number (Tb.N), and trabecular thickness (Tb.Th) under OVX. In vitro, DEC1 knockdown increased RUNX2 expression but impaired osteoblast differentiation, with reduced ALP, Osterix, and Osteocalcin expression. ChIP-seq confirmed RUNX2 enrichment near transcription start sites (TSS). Osteoclast markers (CD254, TCIRG1, ACP5) were also reduced in DEC1−/− mice. DEC1 regulates bone metabolism by modulating RUNX2 signaling, highlighting its dual role in osteoblast and osteoclast differentiation.