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Project

Identification of metabolic pathways in chondrocytes that promote bone regeneration.

Bone tissue engineering is a promising strategy to heal large bone defects. To enhance bone regeneration, skeletal stem/progenitor cells are seeded together with growth factors onto a biocompatible scaffold. However, one of the key challenges in regenerative medicine is the poor survival and functioning of the grafted cells, which impedes translation of this strategy to clinical practice. Likely, the reduced or even absent vascularity in these large bone defects limits oxygen and nutrient supply, which is however necessary for a proper anabolic bone response. We and others observed that stimulating the implanted skeletal progenitors to develop into chondrocytes enhances bone repair, probably because chondrocytes can survive and function in an avascular environment. Based on our preliminary data we hypothesize that adaptations in cell metabolism mediate these beneficial effects, which will be investigated further in this project. We will characterize the differences in nutrient requirements and metabolism between skeletal progenitors and chondrocytes and prove the importance of chondrocyte-specific metabolism for bone regeneration by a genetic approach. The knowledge gathered from this project will not only improve our insight in the metabolic regulation of chondrocyte fate and function, but will also serve as a blueprint for the development of innovative nutrient-based therapeutic approaches to promote cell survival and anabolic responses during bone regeneration.

Date:1 Jan 2018 →  31 Dec 2021
Keywords:Chondrocytes, Bone regeneration, Skeletal progenitors, Cell metabolism
Disciplines:Laboratory medicine, Palliative care and end-of-life care, Regenerative medicine, Other basic sciences, Other health sciences, Nursing, Other paramedical sciences, Other translational sciences, Other medical and health sciences