Journal
PLOS ONE
Volume 17, Issue 3, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0265893
Keywords
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Funding
- Biomedical Laboratory Research and Development Service of the Veterans Administration Office of Research and Development [1I01BX003901-01A2, 2I01BX001405-05A2]
- National Institutes of Health [P20 GM125503, P01 AG13918]
- University of Arkansas for Medical Sciences Tobacco Funds and Translational Research Institute [239 G1-50893-01, 1UL1 RR-029884]
- University of Arkansas for Medical Sciences Barton Endowment funding [271 G1-51451-99]
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The expression of Scarb1 in osteoblasts does not play an important role in bone homeostasis and is not essential for the effects of PC-OxPL on these cells.
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;Scarb1(fl/fl) mice compared to wild type (WT), Osx1-Cre, or Scarb1(fl/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.
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