Deletion of the scavenger receptor Scarb1 in osteoblast progenitors does not affect bone mass

Abstract

The scavenger receptor class B member 1 (SR-B1 or Scarb1) is a cell surface receptor for high density lipoproteins. It also binds oxidized low density lipoproteins and phosphocholine-containing oxidized phospholipids (PC-OxPL), which adversely affect bone homeostasis. Overexpression of a single chain form of the antigen-binding domain of E06 IgM–a natural antibody that recognizes PC-OxPL–increases trabecular and cortical bone mass in female and male mice by stimulating bone formation. We have previously reported that Scarb1 is the most abundant scavenger receptor for PC-OxPL in calvaria-derived osteoblastic cells. Additionally, bone marrow- and calvaria-derived osteoblasts from Scarb1 knockout mice (Scarb1 KO) are protected from the pro-apoptotic and anti-differentiating effects of OxPL. Previous skeletal analysis of Scarb1 KO mice has produced contradictory results, with some studies reporting elevated bone mass but another study reporting low bone mass. To clarify the role of Scarb1 in osteoblasts, we deleted Scarb1 specifically in cells of the osteoblast lineage using Osx1-Cre transgenic mice. We observed no difference in bone mineral density measured by DXA in either female or male Osx1-Cre;Scarb1fl/fl mice compared to wild type (WT), Osx1-Cre, or Scarb1fl/fl littermate controls. Additionally, microCT analysis of 6-month-old females and 7-month-old males did not detect any difference in trabecular or cortical bone mass between genotypes. These results indicate that expression of Scarb1 in cells of the osteoblast lineage does not play an important role in bone homeostasis and, therefore, it is not essential for the effects of PC-OxPL on these cells.

RETRACTED: Deletion of the scavenger receptor Scarb1 in myeloid cells does not affect bone mass

“…To delete Scarb1 in monocytes and macrophages, we crossed mice Scarb1 fl/fl mice [ 12 ] with transgenic mice expressing Cre recombinase under the control of LysM-Cre regulatory elements (LysM-Cre mice) [ 15 ]. The phenotype of LysM-Cre;Scarb1 fl/fl mice was compared with Scarb1 fl/fl littermate controls.…”

“…We had initially hypothesized that Scarb1 was an essential mediator of the pro-apoptotic effects of PC-OxPLs on osteoblasts [ 4 ]. However, our previous work showed that deletion of Scarb1 in osteoblastic lineage cells did not affect bone mass or architecture, demonstrating that Scarb1 does not mediate the deleterious effects of PC-OxPLs on osteoblasts or bone [ 12 ]. Therefore we tested the alternative possibility that PC-OxPLs may exert their anti-osteogenic effects via activation of Scarb1 in macrophages [ 13 ].…”

“…The mouse line harboring the Scarb1 conditional allele has been previously described [ 12 , 14 ]. To delete Scarb1 in the entire myeloid lineage, Scarb1 floxed mice were crossed with LysM-Cre mice, purchased from Jackson Laboratories (stock number 004781) [ 15 ].…”

“…Moreover, osteoblasts from Scarb1 KO mice are protected from the pro-apoptotic and anti-differentiating effects of OxLDL in culture [ 7 ]. However, in our previous work, we found that deletion of Scarb1 in osteoblast lineage cells (targeted by Osx1-Cre) did not affect bone mass or architecture, suggesting that Scarb1 does not mediate the deleterious effects of PC-OxPLs on osteoblasts [ 12 ]. In the present study we have tested the alternative hypothesis that PC-OxPLs may exert their anti-osteogenic effects via activation of Scarb1 in macrophages, possibly leading to increased production anti-osteoblastogenic cytokines, such as TNF-α [ 13 ].…”

Retraction: Deletion of the scavenger receptor Scarb1 in osteoblast progenitors does not affect bone mass

“…Following the publication of this article [ 1 ], an error was identified in regard to the selection of the mouse model.…”