論文

査読有り 国際誌
2012年5月3日

Osteoprotection by semaphorin 3A.

Nature
  • Mikihito Hayashi
  • ,
  • Tomoki Nakashima
  • ,
  • Masahiko Taniguchi
  • ,
  • Tatsuhiko Kodama
  • ,
  • Atsushi Kumanogoh
  • ,
  • Hiroshi Takayanagi

485
7396
開始ページ
69
終了ページ
74
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/nature11000

The bony skeleton is maintained by local factors that regulate bone-forming osteoblasts and bone-resorbing osteoclasts, in addition to hormonal activity. Osteoprotegerin protects bone by inhibiting osteoclastic bone resorption, but no factor has yet been identified as a local determinant of bone mass that regulates both osteoclasts and osteoblasts. Here we show that semaphorin 3A (Sema3A) exerts an osteoprotective effect by both suppressing osteoclastic bone resorption and increasing osteoblastic bone formation. The binding of Sema3A to neuropilin-1 (Nrp1) inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation by inhibiting the immunoreceptor tyrosine-based activation motif (ITAM) and RhoA signalling pathways. In addition, Sema3A and Nrp1 binding stimulated osteoblast and inhibited adipocyte differentiation through the canonical Wnt/β-catenin signalling pathway. The osteopenic phenotype in Sema3a−/− mice was recapitulated by mice in which the Sema3A-binding site of Nrp1 had been genetically disrupted. Intravenous Sema3A administration in mice increased bone volume and expedited bone regeneration. Thus, Sema3A is a promising new therapeutic agent in bone and joint diseases.

リンク情報
DOI
https://doi.org/10.1038/nature11000
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/22522930

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