High expression of 92-kD type IV collagenase (gelatinase B) in the osteoclast lineage during mouse development.
High expression of 92-kD type IV collagenase (gelatinase B) in the osteoclast lineage during mouse development.
复制标题
小鼠发育过程中破骨细胞谱系中 92-kD IV 型胶原酶（明胶酶 B）的高表达。
DOI：
10.1083/jcb.124.6.1091
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发表时间：
1994-03
影响因子：
7.8
通讯作者：
Tryggvason, K
中科院分区：
文献类型：
--
作者：
Reponen, P;Sahlberg, C;Munaut, C;Thesleff, I;Tryggvason, K
产生鼠92 kD IV型胶原酶（明胶酶B）的cDNA克隆，用于测定其一级结构和用于分析体内时间和空间表达。小鼠酶与人类酶具有72%的序列同一性，主要差异是存在一个16个残基的片段，而人类酶则不存在。胚胎和出生后小鼠组织的原位杂交分析显示，破骨细胞系的细胞中存在强烈的信号。在巨噬细胞、多形核白细胞、单核细胞或上皮细胞中没有观察到高于背景的清晰表达，这些细胞已被证明在体外细胞培养物中表达该基因。该基因的表达首先在软骨和牙齿发育的早期阶段在E13观察到，其中在周围的间充质细胞中观察到瞬时信号。在发育后期和出生后，在骨表面的大细胞中观察到强表达。这些细胞可能是破骨细胞，因为它们的位置与TRAP阳性细胞的位置相关。在研究的许多其他组织中未观察到高于背景的信号。结果代表了高度破骨细胞特异性细胞外蛋白酶的第一次证明。结果表明，在胚胎器官的正常发育过程中，92-kD IV型胶原酶在基底膜降解中不起主要作用，而是主要用于骨基质的周转，可能作为明胶酶，用于去除由间质胶原酶产生的变性胶原片段（明胶）。
cDNA clones for murine 92 kD type IV collagenase (gelatinase B) were generated for the determination of its primary structure and for analysis of temporal and spatial expression in vivo. The mouse enzyme has 72% sequence identity with the human counterpart, the major difference being the presence of a 16-residue segment absent from the human enzyme. In situ hybridization analyses of embryonic and postnatal mouse tissues revealed intense signals in cells of the osteoclast cell lineage. Clear expression above background was not observed in macrophages, polymorphonuclear leukocytes, monocytes, or epithelial cells which have been shown to express the gene in vitro in cell cultures. Expression of the gene was first observed at early stage of cartilage and tooth development at E13, where signals were seen transiently in surrounding mesenchymal cells. At later developmental stages and postnatally strong expression was seen in large cells at the surface of bones. These cells were presumably osteoclasts as their location correlated with that of TRAP positive cells. Signals above background were not observed in a number of other tissues studied. The results represent the first demonstration of a highly osteoclast specific extracellular proteinase. The results suggest that during normal development of embryonic organs the 92-kD type IV collagenase does not have a major role in basement membrane degradation, but is rather mainly used for the turnover of bone matrix, possibly as a gelatinase required for the removal of denatured collagen fragments (gelatin) generated by interstitial collagenase.