Erica Scheller, DDS, PhD

Assistant Professor, WashU Medicine

Impact of neuroendocrine signals on bone loss and marrow adiposity in diseases including periodontitis, arthritis, and diabetes

Our lab studies the reciprocal relationships between nerves in bone and skeletal health. Clinically, we are interested in how diabetes (type 1 and type 2) contributes to axon damage and the consequences that this has for bone and bone marrow. We currently have two main aims: 1. To define the relationship between diabetic neuropathy and skeletal disease. This work is funded by the NIH (R00-DE024178, Role: PI). We are working to determine how local nerve damage within the skeleton contributes to bone loss, marrow fat accumulation and fracture risk in patients with diabetes. In addition, we seek to understand whether rescue of axon damage in diabetes is sufficient to promote skeletal health. This study is being performed in collaboration with Hope Center members Jeffrey Milbrandt, Aaron DiAntonio, and Valeria Cavalli. 2. To characterize the innervation of the skeleton by the central and peripheral nervous systems. We were recently funded by the NIH to identify and map the nerves within the skeleton ‘from bone to brain’ as part of the SPARC initiative (U01-DK116317, Role: PI). For the duration of this proposal we will work together with teams from most major peripheral organ systems to generate an anatomical and functional neural map of the major internal organs. This key, fundamental insight will be used to understand how nerves within bone are damaged during disease and how they can be leveraged to promote health and repair of peripheral tissues. This study is being performed in collaboration with Hope Center members John Cirrito and Mark Jacquin and the Hope Animal Surgery core.

Relevance to the mission of the Hope Center

Since 1967, it has been repeatedly noted that clinical neuropathy is correlated with both the prevalence and severity of skeletal disease in diabetic patients. The skeleton is highly innervated and local changes in nerve function have the capacity to regulate bone health and function. However, despite significant correlative evidence linking neuropathy and bone loss in diabetes, the ability of local neuropathic change to contribute to skeletal fragility in these patients remains unexplored. We hypothesize that if we can promote repair of damaged axons in the diabetic skeleton, we can limit fractures and subsequent mortality risk in these patients. Consistent with the goal of the Hope Center, this work will provide novel insight about fundamental mechanisms of neurodegeneration and their impact on health and quality of life. This is accomplished through a multi-disciplinary approach, bridging the fields of neurobiology, physiology, engineering and bone biology.

Figure legend: (A,B) Diabetes is associated with skeletal complications including periodontal bone loss and increased rates of fracture. (C, D) The skeleton and bone marrow are highly innervated by sympathetic efferent (green) and sensory afferent (red) neurons which have the potential to regulate key processes including bone turnover, progenitor cell mobilization, and hematopoiesis. It remains unknown how diabetes contributes to local axon damage with in the bone, and the consequences this has for skeletal health. (E) The skeleton does not exist in isolation and is also connected centrally to peripheral tissues, including white adipose tissue, through central regulatory centers.

More about the Scheller lab