Poster abstracts

Poster number 27 submitted by Angela Blissett

Collagen Regulation: Understanding the Multifaceted Role of Discoidin Domain Receptors

Angela Blissett (Biophysics, Ohio State University), Edward P. Calomeni (Department of Pathology, Ohio State University), Brooke McMichael (Department of Physiology and Cell Biology, Ohio State University), Beth Lee (Department of Physiology and Cell Biology, Ohio State University), Gunjan Agarwal (Department of Biomedical Engineering, Ohio State University)

Abstract:
Bone remodeling is an ongoing maintenance mechanism in human skeletal tissue allowing bone to adapt its composition and architecture to endure mechanical loads and to repair microdamage. However, the underlying mechanisms and molecular markers involved in bone remodeling and repair are not fully understood. Since collagen type 1 is the major component of bone, it is evident that processes regulating collagen deposition and structure are bound to impact bone remodeling. In this proposal we aim to elucidate the role of a collagen binding protein, discoidin domain receptor 1 (DDR1) in regulating bone remodeling and morphology. Our proposed studies build up from our recent publications, where we have elucidated that the extracellular domain (ECD) of DDRs when expressed in osteoblastic cell cultures inhibit collagen fibrillogenesis resulting in reduced collagen fiber diameter and disrupting the banded structure of collagen fibers. In addition DDR ECDs enhance matrix mineralization. Our preliminary results further indicate that collagen fibers formed in the presence of DDRs have a reduced persistence length and elastic modulus. In the current study we aim to understand bone microarchitecture and bone biomechanical properties (mineralization profile and bone elastic modulus map) as a function of DDR1 expression. We utilize wildtype and DDR1 knockout mice and assess bone tissue by µ-CT and electron microscopy. Our results indicate that DDR1 expression is important in the modeling of both cortical and trabecular bone microarchitectures and DDR1 dysfunction in bone leads to decreased mineralization.

Keywords: extracellular matrix, bone, micro-CT