Signals between the brain, the body, and bone. The skeleton is emerging as a key regulator of complex biological processes, including the sending and receiving of endocrine signals. In response to biochemical stimuli, mesenchymal stem cells (MSCs) differentiate into mature, functioning cells. In healthy bone marrow (BM), MSCs differentiate into BM-adipocytes (BMAs) or osteoblasts (OBs) in response to the addition or removal of WNT signaling, respectively. WNT signaling induces RUNX2 expression driving OB differentiation, but inhibition of WNT signaling is required for the differentiation into adipocytes. Sclerostin (SOST), a WNT inhibitor, is emerging as a potential player in the differentiation of BM-MSCs, adding complexity to the regulation of bone marrow adipose tissue (MAT) in response to both adipose (energetic), and bone-derived signals.