Authors: Sung-Jin Kim, Yong Taek Jeong, Se Rok Jeong, Munsu Park, Hye Sun Go, Mi Young Kim, Je Kyung Seong, Ki Woo Kim, Jeong Taeg Seo, Chul Hoon Kim, Ji Hyun Lee, Seok Jun Moon
Published: 2020-05-07
DOI: 10.1038/s12276-020-0419-8
Source: Full article
AbstractNeuronal regulation of energy and bone metabolism is important for body homeostasis. Many studies have emphasized the importance of synaptic adhesion molecules in the formation of synapses, but their roles in physiology still await further characterization. Here, we found that the synaptic adhesion molecule Calsyntenin-3 (CLSTN3) regulates energy and bone homeostasis.Clstn3global knockout mice show reduced body mass with improved leptin sensitivity and increased energy expenditure compared to their wild-type littermates. In addition,Clstn3knockout mice show reduced marrow volume and cortical bone mass without alteration of trabecular bone microarchitecture. This reduced bone mass is not bone cell-autonomous because neither osteoblast- nor osteoclast-specificClstn3knockout mice show bone defects; similarly, in vitro cultures of bothClstn3knockout osteoblasts and osteoclasts do not show any defects. These reduced body and bone mass phenotypes can be attributed instead to neuronal CLSTN3 because they are recapitulated by pan-neuronal but not sympathetic neuron-specific deletion ofClstn3. This study reveals novel physiological functions of neuronalClstn3as a key regulator of energy and bone homeostasis.