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Despite impressive advances in our understanding of the cellular, molecular and genetic mechanisms governing normal skeletal development and homeostasis, diseases of the skeleton, including osteoporosis, osteoarthritis, fracture repair failure, bone cancer, and periodontitis continue to be major contributors to adult morbidity and mortality. By bringing together experts in signal transduction, extracellular matrix (ECM) biology, stem cell biology, developmental biology, molecular genetics, physiology, endocrinology, aging, and emerging technologies, the 2020 Bones and Teeth GRC hopes to capture the tremendous momentum and progress in the field, inspire new research directions, and foster new collaborations aimed at advancing therapeutic development in the skeletal arena. The theme of the 2020 Bones and Teeth GRC is "The Life of the Skeleton". Starting with an introduction to signaling circuits, stem cells, and ECM, we examine the events directing skeletal homeostasis in chronological order, and at specific temporal inflection points compare and contrast the appendicular, axial and craniofacial skeletal responses. We also discuss emerging technologies that allow us to investigate skeletal biology in new ways, and end our meeting by focusing on whether repair/regeneration of adult skeletal tissues is a return to principles that govern embryonic skeletal development, or representative of a new stage of skeletal biology, a controversial topic vital to development of successful therapeutic approaches in the adult skeleton.