Skip to main content

Research Repository

Advanced Search

Bidirectional regulation of bone formation by exogenous and osteosarcoma-derived Sema3A

De Ridder, D; Marino, S; Bishop, R T; Renema, N; Chenu, C; Heymann, D; Idris, A I

Authors

D De Ridder

S Marino

R T Bishop

N Renema

C Chenu

D Heymann

A I Idris



Abstract

Semaphorin 3A (Sema3A), a secreted member of the Semaphorin family, increases osteoblast differentiation, stimulates bone formation and enhances fracture healing. Here, we report a previously unknown role of Sema3A in the regulation of ectopic bone formation and osteolysis related to osteosarcoma. Human recombinant (exogenous) Sema3A promoted the expression of osteoblastic phenotype in a panel of human osteosarcoma cell lines and inhibited the ability of these cells to migrate and enhance osteoclastogenesis in vitro. In vivo, administration of exogenous Sema3A in mice after paratibial inoculation of KHOS cells increased bone volume in non-inoculated and tumour-bearing legs. In contrast, Sema3A overexpression reduced the ability of KHOS cells to cause ectopic bone formation in mice and to increase bone nodule formation by engaging DKK1/?-catenin signalling. Thus, Sema3A is of potential therapeutic efficacy in osteosarcoma. However, inhibition of bone formation associated with continuous exposure to Sema3A may limit its long-term usefulness as therapeutic agent.

Citation

De Ridder, D., Marino, S., Bishop, R. T., Renema, N., Chenu, C., Heymann, D., & Idris, A. I. (2018). Bidirectional regulation of bone formation by exogenous and osteosarcoma-derived Sema3A. https://doi.org/10.1038/s41598-018-25290-2

Journal Article Type Article
Acceptance Date Apr 18, 2018
Publication Date May 2, 2018
Deposit Date May 15, 2018
Publicly Available Date Nov 21, 2020
Journal Scientific Reports (Nature)
Peer Reviewed Peer Reviewed
Volume 8
Pages 6877
DOI https://doi.org/10.1038/s41598-018-25290-2
Public URL https://rvc-repository.worktribe.com/output/1387401

Files







You might also like



Downloadable Citations