Laboratoire du Métabolisme OsseuxBioMed, Département des Sciences Biologiques Université du Québec à Montréal, Case Postale 8888, Succursale Centre-ville, Montréal, Quebec, Canada H3C 3P8Laboratoire du Métabolisme des LipoprotéinesBioMed, Département des Sciences Biologiques, Université du Québec à Montréal, Montréal, Quebec, Canada H3C 3P8.
Laboratoire du Métabolisme OsseuxBioMed, Département des Sciences Biologiques Université du Québec à Montréal, Case Postale 8888, Succursale Centre-ville, Montréal, Quebec, Canada H3C 3P8Laboratoire du Métabolisme des LipoprotéinesBioMed, Département des Sciences Biologiques, Université du Québec à Montréal, Montréal, Quebec, Canada H3C 3P8
J Endocrinol. 2014 Aug;222(2):277-88. doi: 10.1530/JOE-14-0147. Epub 2014 Jun 13.
A positive correlation between plasma levels of HDL and bone mass has been reported by epidemiological studies. As scavenger receptor class B, type I (SR-BI), the gene product of Scarb1, is known to regulate HDL metabolism, we recently characterized bone metabolism in Scarb1-null mice. These mice display high femoral bone mass associated with enhanced bone formation. As gender differences have been reported in HDL metabolism and SR-BI function, we investigated gender-specific bone alterations in Scarb1-null mice by microtomography and histology. We found 16% greater relative bone volume and 39% higher bone formation rate in the vertebrae from 2-month-old Scarb1-null females. No such alteration was seen in males, indicating gender- and region-specific differences in skeletal phenotype. Total and HDL-associated cholesterol levels, as well as ACTH plasma levels, were increased in both Scarb1-null genders, the latter being concurrent to impaired corticosterone response to fasting. Plasma levels of estradiol did not differ between null and WT females, suggesting that the estrogen metabolism alteration is not relevant to the higher vertebral bone mass in female Scarb1-null mice. Constitutively, high plasma levels of leptin along with 2.5-fold increase in its expression in white adipose tissue were measured in female Scarb1-null mice only. In vitro exposure of bone marrow stromal cells to ACTH and leptin promoted osteoblast differentiation as evidenced by increased gene expression of osterix and collagen type I alpha. Our results suggest that hyperleptinemia may account for the gender-specific high bone mass seen in the vertebrae of female Scarb1-null mice.
流行病学研究报道，血浆高密度脂蛋白（HDL）水平与骨量之间呈正相关。由于清道夫受体 B 类，I 型（SR-BI）是 Scarb1 的基因产物，已知其调节 HDL 代谢，我们最近对 Scarb1 基因敲除小鼠的骨代谢进行了特征描述。这些小鼠表现出股骨骨量增加，与骨形成增强有关。由于 HDL 代谢和 SR-BI 功能存在性别差异，我们通过微断层扫描和组织学研究了 Scarb1 基因敲除小鼠的性别特异性骨改变。我们发现 2 个月大的 Scarb1 基因敲除雌性小鼠的椎骨相对骨体积增加了 16%，骨形成率增加了 39%。而在雄性小鼠中则没有这种变化，这表明骨骼表型存在性别和区域特异性差异。Scarb1 基因敲除的雌雄小鼠的总胆固醇和 HDL 相关胆固醇水平以及 ACTH 血浆水平均升高，后者与禁食时皮质酮反应受损有关。雌雄 Scarb1 基因敲除小鼠的雌二醇血浆水平无差异，表明雌激素代谢改变与雌性 Scarb1 基因敲除小鼠椎骨骨量增加无关。我们还发现，仅在雌性 Scarb1 基因敲除小鼠中，循环中瘦素水平升高，其在白色脂肪组织中的表达增加了 2.5 倍。体外将骨髓基质细胞暴露于 ACTH 和瘦素可促进成骨细胞分化，表现为骨钙素和 I 型胶原α的基因表达增加。我们的研究结果表明，高瘦素血症可能是导致雌性 Scarb1 基因敲除小鼠椎骨骨量增加的性别特异性原因。
