Modeling Snyder-Robinson Syndrome in multipotent stromal cells reveals impaired mitochondrial function as a potential cause for deficient osteogenesis.

ABSTRACT: Patients with Snyder-Robinson Syndrome (SRS) exhibit deficient Spermidine Synthase (SMS) gene expression, which causes neurodevelopmental defects and osteoporosis, often leading to extremely fragile bones. To determine the underlying mechanism for impaired bone formation, we modelled the disease by silencing SMS in human bone marrow - derived multipotent stromal cells (MSCs) derived from healthy donors. We found that silencing SMS in MSCs led to reduced cell proliferation and deficient bone formation in vitro, as evidenced by reduced mineralization and decreased bone sialoprotein expression. Furthermore, transplantation of MSCs in osteoconductive scaffolds into immune deficient mice shows that silencing SMS also reduces ectopic bone formation in vivo. Tag-Seq Gene Expression Profiling show

SUBMITTER: Ramsay AL 

PROVIDER: S-EPMC6817887 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature