Huebner J L, Otterness I G, Freund E M, Caterson B, Kraus V B
Duke University Medical Center, Durham, North Carolina 27710, USA.
Arthritis Rheum. 1998 May;41(5):877-90. doi: 10.1002/1529-0131(199805)41:5<877::AID-ART16>3.0.CO;2-#.
To analyze the in vivo compartmental expression of collagenases 1 and 3 (MMP-1 and MMP-13) in the Hartley guinea pig model of spontaneously occurring osteoarthritis (OA) for the purpose of elucidating their roles in the pathogenesis of OA.
Competitive reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry quantification of messenger RNA (mRNA) and protein levels in medial and lateral tibial cartilage obtained from the knee joints of 2-month-old (no OA) and 12-month-old (OA) guinea pigs.
The patterns of mRNA expression of collagenases 1 and 3 varied with the age of the animal and the compartment of the knee. We also found focal areas of collagenase 1 and collagenase 3 proteins localized to the extracellular matrix of OA lesion sites, coincident with three-quarter/one-quarter collagen cleavage. Collagenase 3 protein was also abundant throughout the medial tibial cartilage of 2-month-old animals.
This represents the first description of bona fide collagenase 1 in a rodent species. Recent evidence, however, based on analysis of mitochondrial DNA homologies, suggests that the guinea pig is not a member of the order Rodentia and may be more closely allied with lagomorphs. This taxonomic controversy leaves open to question the issue of the expression of collagenase 1 in other rodents, such as mice and rats. The presence of active collagenases 1 and 3 at OA lesion sites is consistent with an important role of these enzymes in the cartilage degradation of OA in guinea pigs. The expression of collagenase 3 in medial tibial cartilage from 2-month-old guinea pigs may signify a role of this enzyme in cartilage remodeling with growth and development, or it may represent an early molecular manifestation of OA.
分析胶原酶1和3（基质金属蛋白酶-1和基质金属蛋白酶-13）在自发发生骨关节炎（OA）的哈特利豚鼠模型中的体内分区表达情况，以阐明它们在OA发病机制中的作用。
采用竞争性逆转录-聚合酶链反应（RT-PCR）和免疫组织化学方法，对2月龄（无OA）和12月龄（OA）豚鼠膝关节内侧和外侧胫骨软骨中的信使核糖核酸（mRNA）和蛋白质水平进行定量分析。
胶原酶1和3的mRNA表达模式随动物年龄和膝关节分区的不同而变化。我们还发现胶原酶1和胶原酶3蛋白的局灶性区域定位于OA病变部位的细胞外基质，与四分之三/四分之一的胶原裂解一致。胶原酶3蛋白在2月龄动物的整个内侧胫骨软骨中也很丰富。
这是首次在啮齿动物物种中对真正的胶原酶1进行描述。然而，最近基于线粒体DNA同源性分析的证据表明，豚鼠不是啮齿目动物的成员，可能与兔形目动物关系更密切。这种分类学争议使得胶原酶1在其他啮齿动物（如小鼠和大鼠）中的表达问题存在疑问。OA病变部位存在活性胶原酶1和3与这些酶在豚鼠OA软骨降解中的重要作用一致。2月龄豚鼠内侧胫骨软骨中胶原酶3的表达可能表明该酶在软骨生长和发育重塑中的作用，或者它可能代表OA的早期分子表现。
