Biglycan deficiency interferes with ovariectomy-induced bone loss
Biglycan deficiency interferes with ovariectomy-induced bone loss
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DOI：
10.1359/jbmr.2003.18.12.2152
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发表时间：
2003-12-01
影响因子：
6.2
通讯作者：
Heegaard, AM
中科院分区：
文献类型：
--
作者：
Nielsen, KL;Allen, MR;Heegaard, AM
简介：双糖链蛋白聚糖（bgn）是一种富含于骨骼组织的小型细胞外基质蛋白多糖，缺乏双糖链蛋白聚糖的雄性小鼠出现小梁骨量和骨强度下降。本研究的目的是调查双聚糖缺陷雌性小鼠的骨表型，并研究卵巢切除术（OVX）对雌激素消耗的影响。 材料和方法：对 21 周龄小鼠进行 OVX 或假手术，将其分为四组：wt 假手术组（n = 7）、wt OVX（n = 9）、bgn 缺陷假手术组（n = 10) 和 bgn 缺陷 OVX (n = 10)。手术后4周处死小鼠。通过外周定量计算机断层扫描（pQCT）、生化标志物和组织形态计量学分析骨量和骨转换。结果与结论：与雄性小鼠相比，bgn缺乏对雌性小鼠骨代谢的影响很小，显示出明显的性别差异。然而，当受到 OVX 应激时，雌性 bgn 敲除 (KO) 小鼠对 OVX 诱导的小梁骨丢失具有抵抗力。通过 pQCT 测量，wt 小鼠显示小梁骨矿物质密度降低，小梁骨体积 (BV/TV) 减少，矿物质沉积率增加。相比之下，bgn KO 小鼠在 OVX 后没有检测到显着变化。此外，对骨吸收标记物脱氧吡啶啉的分析显示，与bgn KO假小鼠相比，bgn KO OVX小鼠的骨吸收标记物没有显着增加。血清骨保护素 (OPG) 和 RANKL 的测量结果显示，与 wt 小鼠相比，bgn KO 小鼠的 OPG 水平升高，而 RANKL 水平降低。总之，bgn 缺乏可以防止因雌激素消耗而导致的小梁骨转换增加和骨丢失，支持 bgn 在骨中具有双重作用的概念，它可以调节形成和吸收，最终影响骨转换过程。
Introduction: Biglycan (bgn) is a small extracellular matrix proteoglycan enriched in skeletal tissues, and biglycan-deficient male mice have decreased trabecular bone mass and bone strength. The purpose of this study was to investigate the bone phenotype of the biglycan-deficient female mice and to investigate the effect of estrogen depletion by ovariectomy (OVX).Materials and Methods: OVX or sham operations were performed on 21-week-old mice that were divided into four groups: wt sham (n = 7), wt OVX (n = 9), bgn-deficient sham (n = 10) and bgn-deficient OVX (n = 10). The mice were killed 4 weeks after surgery. Bone mass and bone turnover were analyzed by peripheral quantitative computed tomography (pQCT), biochemical markers, and histomorphometry.Results and Conclusions: In contrast to the male mice, there were only few effects of bgn deficiency on bone metabolism in female mice, showing a clear gender difference. However, when stressed by OVX, the female bgn knockout (KO) mice were resistant to the OVX-induced trabecular bone loss. The wt mice showed a decrease in trabecular bone mineral density by pQCT measurements, a decrease in trabecular bone volume (BV/TV), and an increase in mineral apposition rate. In contrast, no significant changes were detected in bgn KO mice after OVX. In addition, analysis of the bone resorption marker deoxypyridinoline showed no significant increase in the bgn KO OVX mice compared with bgn KO sham mice. Measurements of serum osteoprotegerin (OPG) and RANKL revealed increased levels of OPG and decreased levels of RANKL in the bgn KO mice compared with wt mice. In conclusion, the bgn deficiency protects against increased trabecular bone turnover and bone loss in response to estrogen depletion, supporting the concept that bgn has dual roles in bone, where it may modulate both formation and resorption ultimately influencing the bone turnover process.