Cytoskeletal Regulation and Cell-cell Adhesion Molecules in Bone

Non-healing fractures pose an increasing clinical and economical burden. Osteo-anabolic drugs to prevent osteoporosis-induced fractures and improved bone tissue engineering (BTE) strategies to treat non-unions are much sought for, and will depend on a comprehensive understanding of osteoblast biology. Osteoprogenitor migration to and proper maturation, adhesion and positioning at sites in need of bone formation are indispensible aspects of bone remodeling, repair and regeneration, but the mechanisms underlying these cytoskeleton-centered processes are poorly understood. Therefore, we will here explore the role of two linked intracellular regulators of actin cytoskeletal dynamics and cellular adhesion, namely RhoA and p120ctn, in the behavior, differentiation and functioning of skeletal progenitors. By employing genetically modified mice, in vitro models, and advanced imaging techniques, we will study the cellular and molecular processes regulated by RhoA and p120ctn in osteogenic cells, and assess how these contribute to physiological bone formation and remodeling. In addition, we will test whether deregulation of the cytoskeletal dynamics, by inactivation of RhoA in osteogenic cells, may affect bone regeneration and fracture healing. This work will lead to increased insights in the role and regulation of cytoskeletal dynamics in osteogenic cells, and may have important therapeutic implications for control of bone formation and for BTE, opening doors to future valorization.

Jaar van publicatie:2021

Toegankelijkheid:Closed