RRC ID 21792
著者 Fukuda T, Takeda S, Xu R, Ochi H, Sunamura S, Sato T, Shibata S, Yoshida Y, Gu Z, Kimura A, Ma C, Xu C, Bando W, Fujita K, Shinomiya K, Hirai T, Asou Y, Enomoto M, Okano H, Okawa A, Itoh H.
タイトル Sema3A regulates bone-mass accrual through sensory innervations.
ジャーナル Nature
Abstract Semaphorin 3A (Sema3A) is a diffusible axonal chemorepellent that has an important role in axon guidance. Previous studies have demonstrated that Sema3a(-/-) mice have multiple developmental defects due to abnormal neuronal innervations. Here we show in mice that Sema3A is abundantly expressed in bone, and cell-based assays showed that Sema3A affected osteoblast differentiation in a cell-autonomous fashion. Accordingly, Sema3a(-/-) mice had a low bone mass due to decreased bone formation. However, osteoblast-specific Sema3A-deficient mice (Sema3acol1(-/-) and Sema3aosx(-/-) mice) had normal bone mass, even though the expression of Sema3A in bone was substantially decreased. In contrast, mice lacking Sema3A in neurons (Sema3asynapsin(-/-) and Sema3anestin(-/-) mice) had low bone mass, similar to Sema3a(-/-) mice, indicating that neuron-derived Sema3A is responsible for the observed bone abnormalities independent of the local effect of Sema3A in bone. Indeed, the number of sensory innervations of trabecular bone was significantly decreased in Sema3asynapsin(-/-) mice, whereas sympathetic innervations of trabecular bone were unchanged. Moreover, ablating sensory nerves decreased bone mass in wild-type mice, whereas it did not reduce the low bone mass in Sema3anestin(-/-) mice further, supporting the essential role of the sensory nervous system in normal bone homeostasis. Finally, neuronal abnormalities in Sema3a(-/-) mice, such as olfactory development, were identified in Sema3asynasin(-/-) mice, demonstrating that neuron-derived Sema3A contributes to the abnormal neural development seen in Sema3a(-/-) mice, and indicating that Sema3A produced in neurons regulates neural development in an autocrine manner. This study demonstrates that Sema3A regulates bone remodelling indirectly by modulating sensory nerve development, but not directly by acting on osteoblasts.
巻・号 497(7450)
ページ 490-3
公開日 2013-5-23
DOI 10.1038/nature12115
PII nature12115
PMID 23644455
MeSH Animals Bone Remodeling* Bone and Bones / anatomy & histology Bone and Bones / innervation* Bone and Bones / metabolism* Cell Differentiation Cells, Cultured Female Male Mice Organ Size Osteoblasts / cytology Osteoblasts / metabolism Semaphorin-3A / deficiency Semaphorin-3A / genetics Semaphorin-3A / metabolism* Sensory Receptor Cells / cytology Sensory Receptor Cells / metabolism*
IF 42.779
引用数 169
WOS 分野 CELL BIOLOGY
リソース情報
実験動物マウス RBRC01104 RBRC01106