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OPG-Fc treatment partially rescues low bone mass phenotype in mature Bgn/Fmod deficient mice but is deleterious to the young mouse skeleton.
Journal of Structural Biology ( IF 3 ) Pub Date : 2020-09-17 , DOI: 10.1016/j.jsb.2020.107627
Vardit Kram 1 , Priyam Jani 1 , Tina M Kilts 1 , Li Li 1 , Emily Y Chu 2 , Marian F Young 1
Affiliation  

Biglycan (Bgn) and Fibromodulin (Fmod) are small leucine rich proteoglycans (SLRPs) which are abundant in the extra-cellular matrix (ECM) of mineralized tissues. We have previously generated a Bgn/Fmod double knock-out (DKO) mouse model and found it has a 3-fold increase in osteoclastogenesis compared with Wild type (WT) controls, resulting in a markedly low bone mass (LBM) phenotype. To try and rescue/repair the LBM phenotype of Bgn/Fmod DKO mice by suppressing osteoclast formation and activity, 3- and 26-week-old Bgn/Fmod DKO mice and age/gender matched WT controls were treated with OPG-Fc for 6 weeks after which bone parameters were evaluated using DEXA, micro-computed tomography (μCT) and serum biomarkers analyses. In the appendicular skeleton, OPG-Fc treatment improved some morphometric and geometric parameters in both the trabecular and cortical compartments in Bgn/Fmod DKO female and male mice, especially in the repair module. For many of the skeletal parameters analyzed, the Bgn/Fmod DKO mice were more responsive to the treatment than their WT controls. In addition, we found that OPG-Fc treatment was not able to prevent or ameliorate the formation of ectopic ossification, which are common lesions seen in aged joints and are one of the phenotypical hallmarks of our Bgn/Fmod DKO model. Analysis of skull bones, specifically the occipital bone, showed the treatment recovered some parameters of LBM phenotype in the craniofacial skeleton, more so in the younger rescue module. Using OPG-Fc as treatment alleviated, yet did not completely restore, the severe osteopenia and mineralized tissue structural abnormalities that Bgn/Fmod DKO mice suffer from.



中文翻译:

OPG-Fc 治疗部分挽救了成熟 Bgn/Fmod 缺陷小鼠的低骨量表型,但对幼鼠骨骼有害。

Biglycan (Bgn) 和 Fibromodulin (Fmod) 是富含亮氨酸的小蛋白聚糖 (SLRP),它们在矿化组织的细胞外基质 (ECM) 中含量丰富。我们之前已经生成了Bgn/Fmod双敲除 (DKO) 小鼠模型,发现与野生型 (WT) 对照相比,它的破骨细胞生成增加了 3 倍,导致骨量 (LBM) 表型显着降低。为了尝试通过抑制破骨细胞的形成和活性来挽救/修复Bgn/Fmod DKO 小鼠的 LBM 表型,3 周龄和 26 周龄Bgn/FmodDKO 小鼠和年龄/性别匹配的 WT 对照用 OPG-Fc 治疗 6 周,之后使用 DEXA、微型计算机断层扫描 (μCT) 和血清生物标志物分析评估骨骼参数。在阑尾骨骼中,OPG-Fc 治疗改善了Bgn/Fmod DKO 雌性和雄性小鼠的小梁和皮质隔室中的一些形态测量和几何参数,尤其是在修复模块中。对于分析的许多骨骼参数,Bgn/Fmod DKO 小鼠比它们的 WT 对照对治疗更敏感。此外,我们发现 OPG-Fc 治疗无法预防或改善异位骨化的形成,异位骨化是老年关节中常见的病变,也是我们Bgn/Fmod的表型标志之一DKO 模型。颅骨,特别是枕骨的分析表明,治疗恢复了颅面骨骼中 LBM 表型的一些参数,在年轻的救援模块中更是如此。使用 OPG-Fc 作为治疗可减轻但并未完全恢复Bgn/Fmod DKO 小鼠遭受的严重骨质减少和矿化组织结构异常。

更新日期:2020-09-28
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