Stem cell antigen-1 positive cell-based systemic XXXX @entity2124 gene transfer strategy increases endosteal bone resorption and @entity604 in @entity19 .

@entity1 @entity19 @entity604 @entity2124 @entity7424 @entity3513
BACKGROUND: The present study assesses the effect of the stem cell antigen-1 positive ( @entity3513 (+) ) cell-based @entity1 @entity2124 (hGH) ex vivo gene transfer strategy on endosteal bone mass in the @entity19 . METHODS: Sublethally irradiated recipient @entity19 were transplanted with @entity3513 (+) cells transduced with lentiviral vectors expressing hGH or b-galactosidase control genes. Bone parameters were assessed by micro-computed tomography and histomorphometry. RESULTS: This hGH strategy drastically increased hGH mRNA levels in bone marrow cells and serum @entity7424 ( @entity7424 ) (by nearly 50%, p < 0.002) in hGH recipient @entity19 . Femoral trabecular bone volume of the hGH @entity19 was significantly reduced by 35% (p < 0.002). The hGH @entity19 also had decreased trabecular number (by 26%; p < 0.0001), increased trabecular separation (by 38%; p < 0.0002) and reduced trabecular connectivity density (by 64%; p < 0.001), as well as significantly more osteoclasts (2.5-fold; p < 0.05) and greater osteoclastic surface per bone surface (2.6-fold; p < 0.01). CONCLUSIONS: Targeted expression of hGH in cells of marrow cavity through the @entity3513 (+) cell-based gene transfer strategy increased circulating @entity7424 and decreased endosteal bone mass through an increase in resorption in recipient @entity19 . These results indicate that high local levels of hGH or @entity7424 in the bone marrow microenvironment enhanced resorption, which is consistent with previous findings in @entity19 with targeted bone @entity7424 expression showing that high local @entity7424 expression increased bone remodeling, favoring a net @entity604 . Thus, GH and/or @entity7424 would not be an appropriate transgene for use in this @entity3513 cell-based gene transfer strategy to promote endosteal bone formation. Published 2011 John Wiley _ Sons, Ltd.
