Targeted deletion of the SPARC gene accelerates disc degeneration in the aging mouse
Targeted deletion of the SPARC gene accelerates disc degeneration in the aging mouse
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DOI：
10.1369/jhc.5a6687.2005
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发表时间：
2005-09-01
影响因子：
3.2
通讯作者：
Hanley, EN
中科院分区：
文献类型：
--
作者：
Gruber, HE;Sage, EH;Hanley, EN
SPARC（分泌蛋白，酸性，富含半胱氨酸）是一种存在于椎间盘中的基质细胞蛋白；在人类中，SPARC 水平随着衰老和退化而降低。在这项研究中，我们询问小鼠 SPARC 的靶向删除是否会影响椎间盘形态。对 0.3-21 个月大的 SPARC 缺失小鼠和野生型 (WT) 小鼠进行了研究。对 2 个月大的 SPARC 无效小鼠的脊柱进行放射学检查，发现楔形、终板钙化和硬化，这些特征在年龄匹配的 WT 脊柱中不存在。 3 个月大的 SPARC-null 小鼠的椎间盘比 WT 动物的椎间盘具有更多数量的环细胞（1884.6 +/- 397.9 [平均值 +/- SD] vs 1500.2 +/- 188.2，p=0.031）。到 19 个月时，SPARC-null 小鼠的椎间盘含有比 WT 小鼠更少的细胞（1383.6 +/- 363.3 vs 1466.8 +/- 148.0，p=0.033）。正中矢状棘的组织学显示 14-19 个月龄 SPARC 缺失小鼠的下腰椎间盘突出；相反，在 WT 年龄匹配的动物中没有发现疝气。超微结构研究显示，WT 纤维环中的胶原纤维直径均匀，而 SPARC 无效的椎间盘纤维尺寸可变，边缘不规则。与在 SPARC 无效小鼠的其他组织中观察到的结缔组织缺陷一致，我们的研究结果支持 SPARC 在椎间盘细胞外基质的产生、组装或维护中的基本作用。
SPARC (secreted protein, acidic, and rich in cysteine) is a matricellular protein that is present in the intervertebral disc; in man, levels of SPARC decrease with aging and degeneration. In this study, we asked whether targeted deletion of SPARC in the mouse influenced disc morphology. SPARC-null and wild-type (WT) mice were studied at 0.3-21 months of age. Radiologic examination of spines from 2-month-old SPARC-null mice revealed wedging, endplate calcification, and sclerosis, features absent in age-matched WT spines. Discs from 3-month-old SPARC-null mice had a greater number of annulus cells than those of WT animals (1884.6 +/- 397.9 [mean +/- SD] vs 1500.2 +/- 188.2, p=0.031). By 19 months discs from SPARC-null mice contained fewer cells than WT counterparts (1383.6 +/- 363.3 vs 1466.8 +/- 148.0, p=0.033). Histology of midsagittal spines showed herniations of lower lumbar discs of SPARC-null mice ages 14-19 months; in contrast, no herniations were seen in WT age-matched animals. Ultrastructural studies showed uniform collagen fibril diameters in the WT annulus, whereas in SPARC-null disc fibrils were of variable size with irregular margins. Consistent with the connective tissue deficits observed in other tissues of SPARC-null mice, our findings support a fundamental role for SPARC in the production, assembly, or maintenance of the disc extracellular matrix.