Serotonin Rising — The Bone, Brain, Bowel Connection

In a recent article, Yadav et al.1 elucidated the regulation of gut-produced serotonin by low-density lipoprotein receptor–related protein 5 (Lrp5) and the deleterious effect of serotonin on bone mass. This discovery reflects the rapid advances taking place in bone biology and lends support to three newly understood facts about skeletal physiology.The first fact relates to the preeminence, in skeletal acquisition and maintenance, of a signaling pathway consisting of the mammalian homologue of wingless in drosophila (Wnt), Lrp5 or Lrp 6, and β-catenin. This pathway's importance was firmly established through clinical observations from gain-of-function and loss-of-function mutations in the LRP5 . . .