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

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.