Université de Lyon and Institut National de la Santé et de la Recherche Médicale Unité 890/Institut Fédératif de Recherche 143, Saint-Etienne, France.
Endocrinology. 2010 Nov;151(11):5103-13. doi: 10.1210/en.2010-0091. Epub 2010 Sep 15.
Bone sialoprotein (BSP) belongs to the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, whose members play multiple and distinct roles in the development, turnover, and mineralization of bone and dentin. The functions of BSP in bone remodeling are not yet well established. We previously showed that BSP knockout (BSP(-/-)) mice exhibit a higher trabecular bone volume, concomitant with lower bone remodeling, than wild-type (BSP(+/+)) mice. To determine whether bone turnover can be stimulated in the absence of BSP, we subjected BSP(+/+) and BSP(-/-) mice to catabolic [ovariectomy (OVX)] or anabolic (intermittent PTH administration) hormonal challenges. BSP(-/-) mice progressively develop hypocalcemia and high serum PTH between 2 and 4 months of age. Fifteen and 30 d after OVX, microtomography analysis showed a significant decrease of trabecular bone volume in tibiae of both genotypes. Histomorphometric parameters of bone formation and resorption were significantly increased by OVX. PTH treatment resulted in an increase of trabecular thickness and both bone formation and resorption parameters at all skeletal sites in both genotypes and a decrease of trabecular bone volume in tibiae of BSP(+/+) but not BSP(-/-) mice. PTH increased cortical thickness and bone area in BSP(+/+) but not BSP(-/-) mice and stimulated the bone formation rate specifically in the endosteum of BSP(+/+) mice and the periosteum of BSP(-/-) mice. PTH enhanced the expression of RANKL, MEPE, and DMP1 in both genotypes but increased OPG and OPN expression only in BSP(-/-) mice. In conclusion, despite the low basal turnover, both catabolic and anabolic challenges increase bone formation and resorption in BSP(-/-) mice, suggesting that compensatory pathways are operative in the skeleton of BSP-deficient mice. Although up-regulation of one or several other SIBLINGs is a possible mechanism, further studies are needed to analyze the interplay and cross-regulation involved in compensating for the absence of BSP.
骨涎蛋白（BSP）属于小整合素结合配体，N-连接糖蛋白（SIBLING）家族，其成员在骨骼和牙本质的发育、周转和矿化中发挥多种不同的作用。BSP 在骨重塑中的功能尚未得到很好的确立。我们之前的研究表明，BSP 敲除（BSP(-/-)）小鼠表现出比野生型（BSP(+/+)）小鼠更高的小梁骨体积，同时伴有更低的骨重塑。为了确定在没有 BSP 的情况下是否可以刺激骨转换，我们对 BSP(+/+)和 BSP(-/-)小鼠进行了分解代谢[卵巢切除术（OVX）]或合成代谢（间歇性 PTH 给药）激素挑战。BSP(-/-)小鼠在 2 至 4 个月龄时逐渐出现低钙血症和高血清 PTH。OVX 后 15 和 30 天，微断层扫描分析显示两种基因型的胫骨小梁骨体积均显著减少。骨形成和吸收的组织形态计量学参数均显著增加。PTH 治疗导致所有骨骼部位的小梁厚度以及骨形成和吸收参数增加，BSP(+/+)小鼠的胫骨小梁骨体积减少，但 BSP(-/-)小鼠没有。PTH 增加了 BSP(+/+)但不是 BSP(-/-)小鼠的皮质厚度和骨面积，并刺激了 BSP(+/+)小鼠的骨内膜和 BSP(-/-)小鼠的骨外膜的骨形成率。PTH 增强了两种基因型的 RANKL、MEPE 和 DMP1 的表达，但仅在 BSP(-/-)小鼠中增加了 OPG 和 OPN 的表达。总之，尽管基础转化率较低，但分解代谢和合成代谢挑战都会增加 BSP(-/-)小鼠的骨形成和吸收，这表明补偿途径在 BSP 缺乏小鼠的骨骼中起作用。虽然上调一种或几种其他 SIBLINGs 是一种可能的机制，但需要进一步研究来分析涉及补偿 BSP 缺失的相互作用和交叉调节。
