Absence of bone sialoprotein (BSP) impairs primary bone formation and resorption: The marrow ablation model under PTH challenge

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• 作者：Ndé ; ye Mariè ; me Wade-Gueye^a ; ^b ; ^c ; Maya Boudiffa^a ; ^b ; ^c ; Arnaud Vanden-Bossche^a ; ^b ; ^c ; Norbert Laroche^a ; ^b ; ^c ; Jane E. Aubin^d ; Laurence Vico^a ; ^b ; ^c ; Marie-Hé ; lè ; ne Lafage-Proust^a ; ^b ; ^c ; Luc Malaval^a ; ^b ; ^c ; ^{luc.malaval@univ-st-etienne.fr}
• 关键词：Bone sialoprotein ; SIBLING proteins ; Bone modeling ; Bone marrow ablation ; Primary bone
• 刊名：Bone
• 出版年：2012
• 期刊代码：39_87563282
• 类别：med
• 出版时间：May, 2012
• 卷：50
• 期：5
• 页码：1064-1073
• 文件大小：1715 K

摘要

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鈭?鈭?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鈭?鈭?mice, and 7 days post surgery 渭CT analysis showed vigorous new bone formation in the shaft of BSP+/+ animals but much less in BSP鈭?鈭?mice. After 14 days, the volume of medullary bone was significantly decreased as expected in BSP+/+ mice, while it remained stable in the BSP鈭?鈭? Osteoid thickness and surface were higher in BSP鈭?鈭?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鈭?鈭?than in BSP+/+ mice. PTH treatment maintained the volume of medullary bone up to 12 days after ablation in BSP+/+ mice, but failed to do so in BSP鈭?鈭?mice. PTH significantly increased bone formation rate in both genotype, while it reduced osteoclast number and surface in BSP+/+, but not in BSP鈭?鈭?medullary bone. In summary, medullary bone formation after marrow ablation is blunted in BSP鈭?鈭?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.