Anti-Calcitonin Receptor monoclonal antibody, clone 21/00-A3-14-13

To understand hindbrain pathways involved in the control of food intake, we examined roles for calcitonin receptor (CALCR)-containing neurons in the NTS. Ablation of NTS Calcr abrogated the long-term suppression of food intake, but not aversive responses, by CALCR agonists. Similarly, activating Calcr(NTS) Ts neurons decreased food intake and body weight but (unlike neighboring Cck(NTS) cells) failed to promote aversion, revealing that Calcr(NTS) Ts neurons mediate a non-aversive suppression of food intake. While both Calcr(NTS) and Cck(NTS) neurons decreased feeding via projections to the PBN, Cck(NTS) cells activated aversive CGRP PM cells while Calcr(NTS) Ts cells activated distinct non-CGRP PBN cells. Hence, Calcr(NTS) Ts cells suppress feeding via non-aversive, non-CGRP PBN targets. Additionally, silencing Calcr(NTS) Ts cells blunted food intake suppression by gut peptides and nutrients, increasing food intake and promoting obesity. Hence, Calcr(NTS) Ts neurons define a hindbrain system that participates in physiological energy balance and suppresses food intake without activating aversive systems.

Glucocorticoid (GC) therapy decreases bone mass and increases the risk of fractures. We investigated interactions between the GC dexamethasone (DEX) and the bone resorptive agents 1,25(OH)(2)-vitamin D-3 (D3) and parathyroid hormone (PTH) on osteodastogenesis. We observed a synergistic potentiation of osteoclast progenitor cell differentiation and formation of osteoclasts when DEX was added to either D3- or PTH-treated mouse bone marrow cell (BMC) cultures. Cotreatment of DEX with D3 or PTH increased gene encoding calcitonin receptor (Calcr), acid phosphatase 5, tartrate resistant (Acp5), cathepsin K (Ctsk), and TNF superfamily member 11 (Tnfsf11) mRNA, receptor activator of NF-kappa B ligand protein (RANKL), numbers of osteoclasts on plastic, and pit formation and release of C-terminal fragment of type I collagen from cells cultured on bone slices. Enhanced RANKL protein expression caused by D3 and DEX was absent in BMC from mice in which the GC receptor (GR) was deleted in stromal cells/osteoblasts. Synergistic interactions between DEX and D3 on RANKL and osteodast formation were present in BMC from mice with attenuated GR dimerization. These data demonstrate that the GR cooperates with D3 and PTH signaling, causing massive osteoclastogenesis, which may explain the rapid bone loss observed with high dosages of GC treatment.