Molecular properties and fibril ultrastructure of types II and XI collagens in cartilage of mice expressing exclusively the α1(IIA) collagen isoform.
Molecular properties and fibril ultrastructure of types II and XI collagens in cartilage of mice expressing exclusively the α1(IIA) collagen isoform.
复制标题
DOI：
10.1016/j.matbio.2013.09.006
复制
发表时间：
2014-02
期刊：
影响因子：
6.9
通讯作者：
Fernandes, Russell J.
中科院分区：
文献类型：
--
作者：
McAlinden, Audrey;Traeger, Geoffrey;Hansen, Uwe;Weis, Mary Ann;Ravindran, Soumya;Wirthlin, Louisa;Eyre, David R.;Fernandes, Russell J.
关键词：
到目前为止，还没有可用的生物学工具来确定完全源自 IIA 型前胶原异构体的交联胶原纤维网络是否可以在软骨细胞外基质 (ECM) 中形成。最近，产生了纯合敲入转基因小鼠（Col2a1+ex2，ki/ki），它们在出生后发育期间专门表达 IIA 前胶原亚型，而通常存在于野生型小鼠 ECM 中的 IIB 型前胶原不存在。这些 Col2a1 同工型之间的差异在于外显子 2 的包含 (IIA) 或排除 (IIB)，其以发育调控方式选择性剪接。具体而言，软骨祖细胞主要合成 IIA mRNA 亚型，而分化软骨细胞主要产生 IIB mRNA 亚型。最近对 Col2a1+ex2 小鼠的表征令人惊讶地表明，选择性剪接的破坏不会影响明显的软骨形成。在本研究中，生化分析表明，从 ki/ki 小鼠肋骨软骨中提取的 IIA 型胶原蛋白可以形成均聚物，该均聚物主要通过羟赖氨酰吡啶啉 (HP) 交联来稳定，其水平不同于野生型肋骨软骨。研究结果表明，完全源自 IIA 型前胶原分子的成熟 II 型胶原蛋白可以与 XI 型胶原蛋白形成异源原纤维，并有助于软骨结构和功能。还形成了具有 XI 型胶原的杂聚物。电子显微镜显示 ki/ki 小鼠肋骨软骨中主要是薄的 IIA 型胶原原纤维。纯化的 XI 型胶原蛋白的免疫沉淀和质谱分析揭示了 α1(XI)α2(XI)α1(IIA) 链的异三聚体分子组成，其中 α1(IIA) 链是 α3(XI) 链的 IIA 形式。由于 XI 型胶原蛋白的 N 前肽调节软骨中 II 型胶原原纤维的直径，因此外显子 2 编码的 IIA 球状结构域的保留会在结构上改变 XI 型胶原蛋白的 N 前肽。这种结构变化可能随后影响 XI 型胶原蛋白的调节功能，导致本研究中观察到的胶原原纤维和交联差异。
Until now, no biological tools have been available to determine if a cross-linked collagen fibrillar network derived entirely from type IIA procollagen isoforms, can form in the extracellular matrix (ECM) of cartilage. Recently, homozygous knock-in transgenic mice (Col2a1+ex2, ki/ki) were generated that exclusively express the IIA procollagen isoform during post-natal development while type IIB procollagen, normally present in the ECM of wild type mice, is absent. The difference between these Col2a1 isoforms is the inclusion (IIA) or exclusion (IIB) of exon 2 that is alternatively spliced in a developmentally regulated manner. Specifically, chondroprogenitor cells synthesize predominantly IIA mRNA isoforms while differentiated chondrocytes produce mainly IIB mRNA isoforms. Recent characterization of the Col2a1+ex2 mice has surprisingly shown that disruption of alternative splicing does not affect overt cartilage formation. In the present study, biochemical analyses showed that type IIA collagen extracted from ki/ki mouse rib cartilage can form homopolymers that are stabilized predominantly by hydroxylysyl pyridinoline (HP) cross-links at levels that differed from wild type rib cartilage. The findings indicate that mature type II collagen derived exclusively from type IIA procollagen molecules can form hetero-fibrils with type XI collagen and contribute to cartilage structure and function. Heteropolymers with type XI collagen also formed. Electron microscopy revealed mainly thin type IIA collagen fibrils in ki/ki mouse rib cartilage. Immunoprecipitation and mass spectrometry of purified type XI collagen revealed a heterotrimeric molecular composition of α1(XI)α2(XI)α1(IIA) chains where the α1(IIA) chain is the IIA form of the α3(XI) chain. Since the N-propeptide of type XI collagen regulates type II collagen fibril diameter in cartilage, the retention of the exon 2-encoded IIA globular domain would structurally alter the N-propeptide of type XI collagen. This structural change may subsequently affect the regulatory function of type XI collagen resulting in the collagen fibril and cross-linking differences observed in this study.
登录
查看更多内容
影响因子：
7.8
作者：
Hagg, R;Bruckner, P;Hedbom, E
通讯作者：
Hedbom, E
影响因子：
4.4
作者：
ALAKOKKO, L;PROCKOP, DJ
通讯作者：
PROCKOP, DJ
影响因子：
4.8
作者：
Eyre, David R.;Weis, Mary Ann;Wu, Jiann-Jiu
通讯作者：
Wu, Jiann-Jiu
影响因子：
4.8
作者：
Fernandes, RJ;Hirohata, S;Apte, SS
通讯作者：
Apte, SS
DOI：
10.1016/s0006-291x(79)80024-8
发表时间：
1979-01-01
影响因子：
3.1
作者：
BURGESON, RE;HOLLISTER, DW
通讯作者：
HOLLISTER, DW