Expression of ADAMTS4 (aggrecanase-1) in human osteoarthritic cartilage
Expression of ADAMTS4 (aggrecanase-1) in human osteoarthritic cartilage
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DOI：
10.1111/j.1440-1827.2007.02167.x
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发表时间：
2007-11-01
影响因子：
2.2
通讯作者：
Okada, Yasunori
中科院分区：
文献类型：
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作者：
Naito, Satoko;Shiomi, Takayuki;Okada, Yasunori
具有血小板反应蛋白基序的去整合素和金属蛋白酶（ADAMTS）1、4、5、8、9和15，ADAMTS基因家族的成员，具有在特定位点降解主要软骨蛋白聚糖聚集蛋白聚糖的能力，因此被称为“聚集蛋白聚糖酶”。这些ADAMTS物种的表达进行了检查，在人类骨关节炎关节软骨的逆转录聚合酶链反应。结果表明ADAMTS4在骨关节炎软骨中的表达占优势，而ADAMTS5在骨关节炎软骨和正常软骨中组成性表达。ADAMTS9主要在正常软骨中表达，而ADAMTS1、8和15在骨关节炎或正常软骨中没有或可忽略不计地表达。ADAMTS4的原位杂交结果显示，骨关节炎软骨细胞表达ADAMTS4的mRNA。两个单克隆抗体ADAMTS4的开发，并immunolocalized ADAMTS4的软骨细胞中的蛋白聚糖耗尽区的骨关节炎软骨，显示出直接相关的Mankin评分。免疫印迹法表明，在软骨细胞培养基和骨关节炎软骨组织匀浆中的主要蛋白带为58 kDa。这些数据表明，在六种ADAMTS中，ADAMTS4主要以活性形式在骨关节炎软骨中表达，并表明ADAMTS4可能在人骨关节炎软骨中的聚集蛋白聚糖降解中起重要作用。
A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)1, 4, 5, 8, 9 and 15, members of the ADAMTS gene family, have the ability to degrade a major cartilage proteoglycan, aggrecan, at the specific sites, and thus are called 'aggrecanases'. The expression of these ADAMTS species was examined in human osteoarthritic articular cartilage on reverse transcription-polymerase chain reaction. The results demonstrated the predominant expression of ADAMTS4 in osteoarthritic cartilage, while ADAMTS5 was constitutively expressed in osteoarthritic and normal cartilage. ADAMTS9 was expressed mainly in normal cartilage, whereas no or negligible expression of ADAMTS1, 8 and 15 was observed in either osteoarthritic or normal cartilage. In situ hybridization for ADAMTS4 indicated that chondrocytes in osteoarthritic cartilage expressed the mRNA. Two monoclonal antibodies to ADAMTS4 were developed, and immunolocalized ADAMTS4 to chondrocytes in the proteoglycan-depleted zones of osteoarthritic cartilage, showing a direct correlation with the Mankin scores. Immunoblotting indicated a major protein band of 58 kDa in the chondrocyte culture media and osteoarthritic cartilage tissue homogenates. These data demonstrate that among the six ADAMTS species, ADAMTS4 is mainly expressed in an active form in osteoarthritic cartilage, and suggest that ADAMTS4 may play an important role in the degradation of aggrecan in human osteoarthritic cartilage.