The effect of Tlr4 and/or C3 deficiency and of neonatal gene therapy on skeletal disease in mucopolysaccharidosis VII mice.
The effect of Tlr4 and/or C3 deficiency and of neonatal gene therapy on skeletal disease in mucopolysaccharidosis VII mice.
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DOI：
10.1016/j.ymgme.2014.12.305
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发表时间：
2015-02
影响因子：
3.8
通讯作者：
Ponder, Katherine P.
中科院分区：
文献类型：
--
作者：
Xing, Elizabeth M.;Wu, Susan;Ponder, Katherine P.
关键词：
粘多糖贮积症 (MPS) VII 是一种由 β-葡萄糖醛酸酶 (Gusb-/-) 缺乏引起的溶酶体贮积症，并导致糖胺聚糖 (GAG) 积聚。骨骼异常包括长骨发育不良和骨退化。据推测，GAG 可以激活 Toll 样受体 4 (Tlr4) 信号传导和补体途径，导致炎症细胞因子上调，从而抑制生长并导致骨退化。 Gusb-/- 小鼠与 Tlr4 和补体成分 3 (C3) 缺陷小鼠交配，并将双重和三重缺陷小鼠的骨骼表现与纯种 Gusb-/- 小鼠进行比较。射线照片显示，与正常小鼠相比，纯种 Gusb-/- 小鼠的胫骨和股骨较短，股骨较宽。 Tlr4、C3 或 Tlr4/C3 缺陷的 Gusb-/- 小鼠中没有看到任何改善。对关节盂和肱骨的发育不良和骨不规则进行从0（正常）到+3（严重异常）的评分，并测量关节间隙。 Tlr4、C3 或 Tlr4/C3 缺陷的 Gusb-/- 小鼠没有看到任何改善，并且它们的关节间隙仍然异常宽大。与未经治疗的纯种 Gusb-/- 小鼠相比，用静脉内逆转录病毒载体（RV）治疗的新生 Gusb-/- 小鼠股骨更薄，腿更长，关节间隙更窄，但盂肱变性没有改善。我们得出的结论是，Tlr4 和/或 C3 缺乏不能改善骨骼异常，可能涉及其他途径。 RV 治疗可改善骨病的部分而非全部方面。放射线照片可能是未来评估的有效方法，因为它们很容易显示盂肱关节异常。
Mucopolysaccharidosis (MPS) VII is a lysosomal storage disorder caused by the deficiency of the enzyme β-glucuronidase (Gusb-/-) and results in glycosaminoglycan (GAG) accumulation. Skeletal abnormalities include stunted long bones and bone degeneration. GAGs have been hypothesized to activate toll-like receptor 4 (Tlr4) signaling and the complement pathway, resulting in upregulation of inflammatory cytokines that suppress growth and cause degeneration of bone. Gusb-/- mice were bred with Tlr4- and complement component 3 (C3)-deficient mice, and the skeletal manifestations of the doubly- and triply-deficient mice were compared to those of purebred Gusb-/- mice. Radiographs showed that purebred Gusb-/- mice had shorter tibias and femurs, and wider femurs, compared to normal mice. No improvement was seen in Tlr4, C3, or Tlr4/C3-deficient Gusb-/- mice. The glenoid cavity and humerus were scored on a scale from 0 (normal) to +3 (severely abnormal) for dysplasia and bone irregularities, and the joint space was measured. No improvement was seen in Tlr4, C3, or Tlr4/C3-deficient Gusb-/- mice, and their joint space remained abnormally wide. Gusb-/- mice treated neonatally with an intravenous retroviral vector (RV) had thinner femurs, longer legs, and a narrowed joint space compared with untreated purebred Gusb-/- mice, but no improvement in glenohumeral degeneration. We conclude that Tlr4- and/or C3- deficiency fail to ameliorate skeletal abnormalities, and other pathways may be involved. RV treatment improves some but not all aspects of bone disease. Radiographs may be an efficient method for future evaluation, as they readily show glenohumeral joint abnormalities.
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影响因子：
15.9
作者：
BIRKENMEIER, EH;DAVISSON, MT;WAWRZYNIAK, CJ
通讯作者：
WAWRZYNIAK, CJ
早期神经变性与硫酸乙酰肝素在粘多糖糖化IIIB小鼠大脑中的小胶质细胞激活无关。
影响因子：
3.7
作者：
Ausseil, Jerome;Desmaris, Nathalie;Bigou, Stephanie;Attali, Ruben;Corbineau, Sebastien;Vitry, Sandrine;Parent, Mathieu;Cheillan, David;Fuller, Maria;Maire, Irene;Vanier, Marie-Therese;Heard, Jean-Michel
通讯作者：
Heard, Jean-Michel
DOI：
10.1007/s00281-003-0125-3
发表时间：
2003-08-01
期刊：
SPRINGER SEMINARS IN IMMUNOPATHOLOGY
影响因子：
--
作者：
Li, P;Schwarz, EM
通讯作者：
Schwarz, EM
DOI：
10.1073/pnas.192353499
发表时间：
2002-10-01
影响因子：
11.1
作者：
Ponder, KP;Melniczek, JR;Haskins, ME
通讯作者：
Haskins, ME
影响因子：
1.7
作者：
O'Brien, Adam;Bompadre, Viviana;White, Klane K.
通讯作者：
White, Klane K.