Membrane localization of membrane type 1 matrix metalloproteinase by CD44 regulates the activation of pro-matrix metalloproteinase 9 in osteoclasts.
Membrane localization of membrane type 1 matrix metalloproteinase by CD44 regulates the activation of pro-matrix metalloproteinase 9 in osteoclasts.
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DOI：
10.1155/2013/302392
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发表时间：
2013
影响因子：
--
通讯作者：
Ma T
中科院分区：
文献类型：
--
作者：
Chellaiah MA;Ma T
CD44、MT1-MMP 和 MMP9 参与破骨细胞的迁移和骨吸收。本研究旨在确定 CD44 和 MT1-MMP 在 pro-MMP9 激活中的功能关系。我们使用从野生型和 CD44 缺失小鼠中分离的破骨细胞。结果显示，MT1-MMP以多种形式存在于野生型破骨细胞膜中，分子量分别为~63、55和45kDa。 CD44 缺失的破骨细胞在膜和条件培养基中表现出 55kDa 活性 MT1-MMP 形式。它无法激活 pro-MMP9，因为 TIMP2 结合并抑制 CD44 无效破骨细胞中的 MT1-MMP (~55kDa)。通过在野生型破骨细胞中敲除 MT1-MMP，证实了 MT1-MMP 在 pro-MMP9 激活、CD44 表达和迁移中的作用。尽管 MMP9 的敲除抑制了破骨细胞的迁移，但它对 MT1-MMP 活性或 CD44 表达没有影响。这些结果表明CD44和MT1-MMP直接或间接参与pro-MMP9激活的调节。 CD44 的表面表达、MT1-MMP 的膜定位和 pro-MMP9 的激活是破骨细胞迁移过程中必要的事件序列。
CD44, MT1-MMP, and MMP9 are implicated in the migration of osteoclast and bone resorption. This study was designed to determine the functional relationship between CD44 and MT1-MMP in the activation of pro-MMP9. We used osteoclasts isolated from wild-type and CD44-null mice. Results showed that MT1-MMP is present in multiple forms with a molecular mass ~63, 55, and 45 kDa in the membrane of wild-type osteoclasts. CD44-null osteoclasts demonstrated a 55 kDa active MT1-MMP form in the membrane and conditioned medium. It failed to activate pro-MMP9 because TIMP2 binds and inhibits this MT1-MMP (~55 kDa) in CD44-null osteoclasts. The role of MT1-MMP in the activation of pro-MMP9, CD44 expression, and migration was confirmed by knockdown of MT1-MMP in wild-type osteoclasts. Although knockdown of MMP9 suppressed osteoclast migration, it had no effects on MT1-MMP activity or CD44 expression. These results suggest that CD44 and MT1-MMP are directly or indirectly involved in the regulation of pro-MMP9 activation. Surface expression of CD44, membrane localization of MT1-MMP, and activation of pro-MMP9 are the necessary sequence of events in osteoclast migration.
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影响因子：
4.8
作者：
Chellaiah, MA;Biswas, RS;Hruska, KA
通讯作者：
Hruska, KA
影响因子：
4.8
作者：
Chellaiah, MA;Soga, N;Hruska, KA
通讯作者：
Hruska, KA
DOI：
10.1083/jcb.148.4.665
发表时间：
2000-02-21
期刊：
The Journal of cell biology
影响因子：
--
作者：
Chellaiah M;Kizer N;Silva M;Alvarez U;Kwiatkowski D;Hruska KA
通讯作者：
Hruska KA
膜型1基质金属蛋白酶切割CD44并促进细胞迁移。
影响因子：
7.8
作者：
Kajita, M;Itoh, Y;Chiba, T;Mori, H;Okada, A;Kinoh, H;Seiki, M
通讯作者：
Seiki, M
影响因子：
4.8
作者：
Hernandez-Barrantes, S;Toth, M;Fridman, R
通讯作者：
Fridman, R