Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 May 3;485(7396):69-74.
doi: 10.1038/nature11000.

Osteoprotection by semaphorin 3A

Mikihito Hayashi  1 , Tomoki Nakashima, Masahiko Taniguchi, Tatsuhiko Kodama, Atsushi Kumanogoh, Hiroshi Takayanagi
Affiliations

Osteoprotection by semaphorin 3A

Mikihito Hayashi et al. Nature. .

Abstract

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.

PubMed Disclaimer

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Trends Mol Med. 2005 Feb;11(2):76-81 - PubMed
    1. Bone. 1995 Aug;17(2 Suppl):93S-98S - PubMed
    1. Biochem Biophys Res Commun. 1998 Jun 29;247(3):610-5 - PubMed
    1. Nat Rev Rheumatol. 2011 Sep 20;7(11):631-8 - PubMed
    1. Nat Med. 2009 Jul;15(7):757-65 - PubMed

Publication types

MeSH terms