The Osteocyte as a Signaling Cell
Osteocytes, former osteoblasts encapsulated by mineralized bone matrix, are far from being passive and metabolically inactive bone cells. Instead, osteocytes are multifunctional and dynamic cells capable of integrating hormonal and mechanical signals and transmitting them to effector cells in bone as well as in distant tissues. Osteocytes are a significant source of molecules that regulate bone homeostasis by integrating mechanical cues and hormonal signals that coordinate the differentiation and function of osteoclasts and osteoblasts. Osteocyte function is altered in rare and common bone diseases, suggesting that osteocyte dysfunction is directly involved in the pathophysiology of disorders affecting the skeleton. Advances in osteocyte biology initiated the development of novel therapeutics interfering with osteocyte secreted molecules. Moreover, osteocytes are targets and key distributors of biological signals mediating the beneficial effects of various bone therapeutics used in the clinic. Herein, we review the most recent discoveries in osteocyte biology demonstrating that osteocytes regulate bone homeostasis and bone marrow fat via paracrine signaling, influence body composition and energy metabolism via endocrine signaling, and contribute to the damaging effects of diabetes mellitus and hematological and metastatic cancers in the skeleton.