Discoidin Receptor 2 Controls Bone Formation and Marrow Adipogenesis

• DOI: 10.1002/jbmr.2893
• Publication Date: 2016-06-24T13:13:01Z
• Authors: Chunxi Ge; Zhengyan Wang; Guisheng Zhao; Binbin Li; Jinhui Liao; Hanshi Sun; Renny T Franceschi
• Keywords: RUNX2

ABSTRACT Cell–extracellular matrix (ECM) interactions play major roles in controlling progenitor cell fate and differentiation. The receptor tyrosine kinase, discoidin domain 2 (DDR2), is an important mediator of between cells fibrillar collagens. DDR2 signals through both ERK1/2 p38 MAP which stimulate osteoblast differentiation bone formation. Here we show that critical for skeletal development marrow to osteoblasts while suppressing adipogenesis. Smallie mice (Ddr2slie/slie), contain a nonfunctional Ddr2 allele, have multiple defects. A progressive decrease tibial trabecular volume/total volume (BV/TV) was observed when wild-type (WT), Ddr2wt/slie, Ddr2slie/slie were compared. These changes associated with reduced number (Tb.N) thickness (Tb.Th) increased spacing (Tb.Sp) males females, but cortical only females. Bone attributed decreased formation rather than osteoclast activity. Significantly, fat adipocyte-specific mRNA expression significantly elevated animals. Additional defects include widened calvarial sutures vertebral bone. To examine the role signaling differentiation, stromal (BMSCs) grown under osteogenic adipogenic conditions. exhibited defective accelerated Changes related activity runt-related transcription factor (RUNX2) PPARγ, factors are controlled by MAPK-dependent phosphorylation. Specifically, from ERK/MAP kinase RUNX2-S319 phosphorylation could be rescued constitutively active phosphomimetic RUNX2 mutant. Also, shown increase transcriptional also increasing PPARγ-S112 phosphorylation, reducing its is, therefore, maintenance suppression adipogenesis vivo these actions PPARγ © 2016 American Society Mineral Research.