Department of Experimental Medicine I, Nikolaus-Fiebiger Centre of Molecular Medicine, University of Erlangen-Nuremberg, 91054 Erlangen, Germany.
Bone. 2012 Mar;50(3):670-80. doi: 10.1016/j.bone.2011.11.017. Epub 2011 Dec 2.
Ucma (Upper zone of growth plate and Cartilage Matrix Associated protein) is a highly conserved tyrosine-sulphated secreted protein of Mw 17 kDa, which is expressed by juvenile chondrocytes. To evaluate the physiological function of this novel cartilage protein, we generated a Ucma-deficient mouse strain by introducing a lacZ/neoR-cassette into the first exon of the Ucma gene. This mutation results in the complete loss of Ucma mRNA and protein expression. Surprisingly, however, although previous in vitro studies implied a role for Ucma in calcification and ossification, these processes were not affected in Ucma-deficient mice during normal development. Likewise, cartilage development was normal. While in previous works Ucma was mainly detected in the cartilage of embryonic and young mice, we detected Ucma expression also in the adult cartilage of the ribs using the lacZ cassette under the control of the Ucma promoter. Moreover, Ucma protein was specifically detected in adult growth plate cartilage by immunohistochemistry. Considering that skeletal development in Ucma-deficient mice is not significantly impaired, protein expression in adult cartilage indicates that Ucma might be involved in skeletal homeostasis and in the mechanical properties of the skeleton during challenging conditions such as ageing or disease.
Ucma(生长板上区和软骨基质相关蛋白)是一种高度保守的酪氨酸硫酸化分泌蛋白,分子量为 17 kDa,由幼年软骨细胞表达。为了评估这种新型软骨蛋白的生理功能,我们通过将 lacZ/neoR-盒插入 Ucma 基因的第一个外显子,产生了 Ucma 缺陷型小鼠品系。该突变导致 Ucma mRNA 和蛋白表达完全缺失。然而,令人惊讶的是,尽管之前的体外研究表明 Ucma 在钙化和骨化过程中发挥作用,但在正常发育过程中,Ucma 缺陷型小鼠的这些过程并未受到影响。同样,软骨发育也正常。虽然在之前的研究中 Ucma 主要在胚胎和幼鼠的软骨中检测到,但我们使用 Ucma 启动子控制下的 lacZ 盒在肋骨的成年软骨中也检测到 Ucma 的表达。此外,免疫组织化学检测到 Ucma 蛋白在成年生长板软骨中特异性表达。考虑到 Ucma 缺陷型小鼠的骨骼发育没有明显受损,成年软骨中的蛋白表达表明 Ucma 可能参与骨骼的动态平衡以及在衰老或疾病等挑战性条件下骨骼的机械性能。