Absence of bone sialoprotein (BSP) impairs primary bone formation and resorption: the marrow ablation model under PTH challenge.
Absence of bone sialoprotein (BSP) impairs primary bone formation and resorption: the marrow ablation model under PTH challenge.
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DOI：
10.1016/j.bone.2012.02.014
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发表时间：
2012-05
期刊：
影响因子：
4.1
通讯作者：
Ndéyé Marième Wade-Guéye;M. Boudiffa;A. Vanden‐Bossche;N. Laroche;J. Aubin;L. Vico;M. Lafage-Proust;L. Malaval
中科院分区：
文献类型：
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作者：
Ndéyé Marième Wade-Guéye;M. Boudiffa;A. Vanden‐Bossche;N. Laroche;J. Aubin;L. Vico;M. Lafage-Proust;L. Malaval
骨唾液酸蛋白（BSP）在早期骨沉积中高表达，可能参与原发性骨矿化。我们之前表明，虽然BSP−/−小鼠具有轻度的继发性骨表型，并且对机械（卸载）和激素（卵巢切除术，甲状旁腺激素（PTH））的挑战有反应，但这些小鼠中涉及原发性骨沉积的皮质骨缺损的修复显着延迟。在本研究中，我们研究了BSP在原发性骨建模的纯模型中的作用。在BSP+/+和BSP−/−小鼠的股骨中通过经骨骺抽吸消融骨髓，术后7天的μCT分析显示BSP+/+动物的骨干中有活跃的新骨形成，但BSP−/−小鼠中的新骨形成要少得多。14天后，BSP+/+小鼠的髓骨体积显著减少，而BSP-/-小鼠的髓骨体积保持稳定。BSP−/−组第7天类骨质厚度和表面较高，表明矿化延迟，而破骨细胞表面和数量在第14天显著较低，这是一个高骨髓骨吸收阶段。在第7天，早期成骨细胞标志物基因（RUNX 2，osterix，碱性磷酸酶，骨桥蛋白）的mRNA表达在两种基因型之间没有差异，而终末分化标志物（MEPE，DMP 1，骨钙素）以及NF-κ B配体受体激活剂（RANKL）和抗酒石酸酸性磷酸酶（TRAP）在BSP−/−小鼠中显著低于BSP+/+小鼠。PTH治疗在BSP+/+小鼠中保持了髓骨体积长达12天，但在BSP−/−小鼠中未能做到这一点。PTH在两种基因型中均显著增加骨形成率，但在BSP+/+中减少破骨细胞数量和表面，而在BSP−/−髓骨中不增加。总之，骨髓消融后骨髓骨形成在BSP−/−小鼠中是钝化的，具有延迟的再吸收和对PTH的反应受损。这些发现证实了BSP在原发性骨化中起关键作用的假设，长期以来一直怀疑其与矿化有关，但在这里延伸到骨沉积和转换。
Bone sialoprotein (BSP) is highly expressed in early bone deposition and may play a part in primary bone mineralization. We previously showed that while BSP−/− mice have a mild secondary bone phenotype and are responsive to mechanical (unloading) and hormonal (ovariectomy, parathyroid hormone (PTH)) challenges, repair of a cortical bone defect, which involves primary bone deposition is significantly delayed in these mice. In the present study, we investigated the role of BSP in a pure model of primary bone modeling. Bone marrow was ablated by trans-epiphysis aspiration in the femora of BSP+/+ and BSP−/− mice, and 7days post surgery μCT analysis showed vigorous new bone formation in the shaft of BSP+/+ animals but much less in BSP−/− mice. After 14days, the volume of medullary bone was significantly decreased as expected in BSP+/+ mice, while it remained stable in the BSP−/−. Osteoid thickness and surface were higher in BSP−/− at day 7, suggesting delayed mineralization, while osteoclast surface and number were significantly lower at day 14, a stage of high medullary bone resorption. At day 7, mRNA expression of early osteoblast marker genes (RUNX2, osterix, alkaline phosphatase, osteopontin) did not differ between the two genotypes, while markers of terminal differentiation (MEPE, DMP1, osteocalcin) as well as receptor activator of NF-kappaB ligand (RANKL) and tartrate-resistant acid phosphatase (TRAP) were significantly lower in BSP−/− than in BSP+/+ mice. PTH treatment maintained the volume of medullary bone up to 12days after ablation in BSP+/+ mice, but failed to do so in BSP−/− mice. PTH significantly increased bone formation rate in both genotype, while it reduced osteoclast number and surface in BSP+/+, but not in BSP−/− medullary bone. In summary, medullary bone formation after marrow ablation is blunted in BSP−/− mice, with delayed resorption and impaired response to PTH. These findings confirm the hypothesis of a crucial role for BSP in primary ossification, which has long been suspected for mineralization, but here extends to bone deposition and turnover.