Cyclophilin B Deficiency Causes Abnormal Dentin Collagen Matrix.
Cyclophilin B Deficiency Causes Abnormal Dentin Collagen Matrix.
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亲环蛋白 B 缺乏会导致牙本质胶原蛋白基质异常。
DOI：
10.1021/acs.jproteome.7b00190
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发表时间：
2017
影响因子：
4.4
通讯作者：
Yamauchi,Mitsuo
中科院分区：
文献类型：
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作者：
Terajima,Masahiko;Taga,Yuki;Cabral,WayneA;Nagasawa,Masako;Sumida,Noriko;Hattori,Shunji;Marini,JoanC;Yamauchi,Mitsuo
亲环素B(CypB)是一种内质网驻留蛋白，调节胶原的折叠，也参与胶原的3-羟化(P3H)和赖氨酸(Lys)羟化。在这项研究中，我们对CypB缺失(KO)小鼠的牙本质I型胶原进行了表征，并与野生型(WT)和杂合子(Het)小鼠进行了比较。质谱分析表明，与WT/Het相比，KO胶原蛋白中P3H的含量明显减少。在α1/α2(I)Lys-87和α1(I)Lys-930这两个螺旋交联点上，KO中的Lys羟化程度显著降低，导致低位羟化的交联键显著增加，而全羟化的交联位显著减少。除α1(I)Lys-87外，KO中羟赖氨酸残基的糖基化程度普遍高于WT/Het。其中一些分子表型与以前报道的其他KO组织不同，表明牙本质通过CypB特异的调控机制。组织学分析显示，KO组前牙本质宽度较大且不规则，胶原纤维稀疏，明显小于WT/Het组。这些结果表明CypB在牙本质基质的形成中起着关键作用，提示隐性成骨不全与尚未被临床检测到的牙本质缺陷之间可能存在关联。
Cyclophilin B (CypB) is an endoplasmic reticulum-resident protein that regulates collagen folding, and also contributes to prolyl 3-hydroxylation (P3H) and lysine (Lys) hydroxylation of collagen. In this study, we characterized dentin type I collagen in CypB null (KO) mice, a model of recessive osteogenesis imperfecta type IX, and compared to those of wild-type (WT) and heterozygous (Het) mice. Mass spectrometric analysis demonstrated that the extent of P3H in KO collagen was significantly diminished compared to WT/Het. Lys hydroxylation in KO was significantly diminished at the helical cross-linking sites, α1/α2(I) Lys-87 and α1(I) Lys-930, leading to a significant increase in the under-hydroxylated cross-links and a decrease in fully hydroxylated cross-links. The extent of glycosylation of hydroxylysine residues was, except α1(I) Lys-87, generally higher in KO than WT/Het. Some of these molecular phenotypes were distinct from other KO tissues reported previously, indicating the dentin-specific control mechanism through CypB. Histological analysis revealed that the width of predentin was greater and irregular, and collagen fibrils were sparse and significantly smaller in KO than WT/Het. These results indicate a critical role of CypB in dentin matrix formation, suggesting a possible association between recessive osteogenesis imperfecta and dentin defects that have not been clinically detected.