Hormonal, paracrine/autocrine as well as mechanical factors regulate Bone remodeling, but multiple neuronal clues appear to be involved as well (PMID: 18410742, PMID: 17440766, PMID: 16132233, PMID: 16054066), in agreement with the homeostatic nature of bone remodeling. We have demonstrated that neurons in the hypothalamus inhibit bone formation by osteoblasts and favor bone resorption by osteoclasts (PMID: 12419242). This function, regulated by the adipocyte-derived hormone leptin, is mediated via the sympathetic nervous system and the beta2-adrenergic receptor expressed by osteoblasts (PMID: 15724149, Figure 1).
Based on these findings, our goal is now to understand the importance of beta2-adrenergic signaling in bone diseases and to determine if one can modify beta2-adrenergic signaling in osteoblasts to improve bone mass. Several mouse genetic models lacking components modulating beta2-adrenergic signaling as well as pharmacological approaches are used in the laboratory to address these questions.