Biglycan regulates bone development and regeneration

Endochondral bone development and regeneration relies on activation and proliferation of periosteum derived-cells (PDCs). Biglycan (Bgn), a small proteoglycan found in extracellular matrix , is known to be expressed in bone and cartilage, however little is known about its influence during bone development. Here we link Bgn with osteoblast maturation starting during embryonic development that with aging affects bone integrity and strength. Bgn gene deletion reduced the inflammatory response after fracture, leading to impaired periostal expansion and callus formation. Using novel 3D scaffold and analyzing newborn bones, we found that Bgn is required for the cartilage-bone transition of PDCs during endochondral bone development. The absence of Bgn led to accelerated bone development with high levels of osteopontin which appeared to be detrimental to the structural integrity of the bone. Collectively, our study identifies Bgn as an important factor in PDCs activation during bone development and bone regeneration after fracture. Overall design: In this study, we isolated cells from WT and Bgn KO embryos (E16.5) and newborn (P-3) bones Femurs from 6-7 week-old WT or Bgn KO male mice were fractured and collected for bulk RNAseq 3 days after fracture. For each mouse one femure was fractured and the seconed femure sereved as the control un-fractured bone. contributor: NIDCD/NIDCR Genomics and Computational Biology Core