Center for Bone Biology

ROLE OF THE BRAIN AND SYMPATHETIC NERVOUS SYSTEM ON BONE REMODELING AND CANCER METASTASIS
It has become evident during the last few years that bone remodeling is regulated not only by hormonal and paracrine/autocrine factors, but also by neuronal clues (PMID: 18410742, PMID: 17440766, PMID: 16132233, PMID: 16054066). Hypothalamic neurons indeed inhibit bone formation by osteoblasts and favor bone resorption by osteoclasts (PMID: 12419242), via activation of autonomic nerves reaching the bone marrow microenvironment and stimulating the beta2-adrenergic receptor (β2AR) expressed by osteoblasts (PMID: 15724149). This work, and data from independent groups, position βAR signaling in osteoblasts as a major regulatory pathway impacting not only osteoblast proliferation, but also osteoclastogenesis, the trafficking of bone marrow hematopoietic cells and energy homeostasis (PMID: 16143109, PMID: 18256599). Therefore, understanding how βAR signaling in osteoblasts is regulated in normal and pathological conditions is of critical importance to design preventive and corrective measures to improve bone health. In that line of thoughts, our current studies aim at understanding if and how sympathetic signals are involved in bone diseases and at determining if one can alter adrenergic signaling to increase bone mass or prevent bone loss. Major diseases related to β2AR signaling and bone under study in our laboratory are glucocorticoid-induced bone loss (PMID:  21266510) osteoporosis, bone cancer metastasis (PMID: 22815651) and depression. Several mouse genetic models lacking components of the β2-adrenergic receptor signaling pathway as well as pharmacological approaches are used in the laboratory to address these questions. This work is funded by the NIH (P.I. Dr. F. Elefteriou)

Sympathetic Team
 
 

Yun Ma	Preston Campbell	Patrick Mulcrone	Guillaume Vignaux	Yuantee Zhu