Fibroblast Growth Factor Receptor Signaling in Maturing Osteoblasts Controls Cell-Matrix Interactions Critical for Osteocyte Survival

Inactivation of fibroblast growth factor receptor 1 (FGFR1) in the mature osteoblast lineage using DMP1-CreER to target a floxed allele of Fgfr1 (FGFR1-CKO) results in extensive osteocyte death. To identify changes in gene expression in response to inactivation of Fgfr1 in vivo, femoral diaphyseal bone was harvested from 16-week-old Control (Fgfr1f/f) and FGFR1-CKO mice following 4 weeks exposure to Tamoxifen and subjected to bulk mRNA sequencing. RNA sequencing demonstrated reduced expression of extracellular matrix (ECM) genes and neuronal regulatory genes, and differential expression of apoptosis regulatory genes. These data demonstrate that signaling through FGF receptor may be directly required for ECM remodeling and osteocyte projection formation, and loss of FGFR signaling causes retention of an osteoblast-like gene expression signature and apoptosis of bone-embedded cells.