Biglycan regulates bone development and regeneration

Reut Shainer; Vardit Kram; Tina M Kilts; Li Li; Andrew D Doyle; Inbal Shainer; Daniel Martin; Carl G Simon Jr; Jinyang Zeng-Brouwers; Liliana Schaefer; Marian F Young; Genomics and Computational Biology Core

doi:10.3389/fphys.2023.1119368

Biglycan regulates bone development and regeneration

Front Physiol. 2023 Feb 16;14:1119368. doi: 10.3389/fphys.2023.1119368. eCollection 2023.

Affiliations

¹ Molecular Biology of Bones and Teeth Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, United States.
² NIDCR Imaging Core, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, United States.
³ Department Genes-Circuits-Behavior, Max Planck Institute for Biological Intelligence, Martinsried, Germany.
⁴ NIDCD/NIDCR Genomics and Computational Biology Core, National Institutes of Health, Bethesda, MD, United States.
⁵ Biosystems and Biomaterials Division, National Institute of Standards and Technology, Gaithersburg, MD, United States.
⁶ Pharmazentrum Frankfurt, Institut für Allgemeine Pharmakologie und Toxikologie, Klinikum der Goethe-Universität Frankfurt am Main, Frankfurt, Germany.

Abstract

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 biglycan with osteoblast maturation starting during embryonic development that later affects bone integrity and strength. Biglycan gene deletion reduced the inflammatory response after fracture, leading to impaired periosteal expansion and callus formation. Using a novel 3D scaffold with PDCs, we found that biglycan could be important for the cartilage phase preceding bone formation. The absence of biglycan 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 biglycan as an influencing factor in PDCs activation during bone development and bone regeneration after fracture.

Keywords: biglycan; bone; cartilage; extracellular matrix; fracture; periosteum.

Grant support

The research was supported in part by the Intramural Research Program of the NIH, NIDCR Molecular Biology of Bones and Teeth Section (Z01DE000379), Veterinary Resources Core (ZICDE000740) Genomics and Computational Biology Core (ZIC DC000086), Imaging Core (ZIC DE000750) Combined Technical Research Core (ZIC DE000729). This work utilized the computational resources of the NIH HPC Biowulf cluster (http://hpc.nih.gov). IS work was supported by the Alexander von Humboldt foundation research fellowship. LS work was supported by the German Research Council (SFB 1039, project B02, SFB 1177, 259130777, project E02, and the CardioPulmonary Institute (CPI), EXC 2026, Project ID: 390649896.