Collagen XXVII Organises the Pericellular Matrix in the Growth Plate

In order to characterise the function of the novel fibrillar type XXVII collagen, a series of mice expressing mutant forms of the collagen were investigated. Mice harboring a glycine to cysteine substitution in the collagenous domain were phenotypically normal when heterozygote and displayed a mild disruption of growth plate architecture in the homozygous state. Mice expressing an 87 amino acid deletion in the collagenous domain of collagen XXVII were phenotypically normal as heterozygotes whereas homozygotes exhibited a severe chondrodysplasia and died perinatally from a lung defect. Animals expressing the 87 amino acid deletion targeted specifically to cartilage were viable but severely dwarfed. The pericellular matrix of proliferative chondrocytes was disrupted and the proliferative cells exhibited a decreased tendency to flatten and form vertical columns. Collagen XXVII plays an important structural role in the pericellular extracellular matrix of the growth plate and is required for the organisation of the proliferative zone.

为了表征新型原纤维型XXVII胶原（fibrillar type XXVII collagen）的功能，本研究对一系列表达该胶原突变体形式的小鼠开展了实验研究。在胶原结构域中携带甘氨酸向半胱氨酸错义替换的小鼠，杂合子表型正常，纯合子个体则表现出生长板结构的轻度紊乱。而在XXVII胶原的胶原结构域中存在87个氨基酸缺失的小鼠，杂合子表型仍无异常，但纯合子会出现严重的软骨发育不良，并因肺部发育缺陷在围产期死亡。将该87氨基酸缺失突变定向特异性表达于软骨组织的小鼠可正常存活，但体型呈现严重矮小。增殖期软骨细胞的细胞周基质遭到破坏，且增殖细胞扁平化并形成垂直柱结构的趋势显著降低。XXVII胶原在生长板的细胞周细胞外基质中发挥关键的结构支撑功能，且对增殖区的正常组织构建必不可少。