Matrix metalloproteinase 9 and vascular endothelial growth factor are essential for osteoclast recruitment into developing long bones.
Matrix metalloproteinase 9 and vascular endothelial growth factor are essential for osteoclast recruitment into developing long bones.
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DOI：
10.1083/jcb.151.4.879
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发表时间：
2000-11-13
期刊：
影响因子：
--
通讯作者：
Delaissé JM
中科院分区：
文献类型：
--
作者：
Engsig MT;Chen QJ;Vu TH;Pedersen AC;Therkidsen B;Lund LR;Henriksen K;Lenhard T;Foged NT;Werb Z;Delaissé JM
骨发育需要从周围间充质中募集破骨细胞前体，从而允许骨生长的关键事件，如骨髓腔形成、毛细血管侵入和基质重塑。我们证明，明胶酶B/基质金属蛋白酶（MMP）-9缺乏的小鼠表现出破骨细胞募集延迟。组织学分析和专门的侵袭和骨吸收模型表明，MMP-9是破骨细胞和内皮细胞侵入填充骨干核心的不连续矿化肥大软骨所特别需要的。然而，MMP-9以外的MMP是细胞通过新生骨领的未矿化I型胶原所必需的，并且在矿化基质的再吸收中起作用。MMP-9通过MMP-13刺激未矿化软骨的溶解，MMP-13是一种在破骨细胞侵入前在肥大软骨中高度表达的胶原酶。肥大软骨还表达血管内皮生长因子（VEGF），其与细胞外基质结合并通过MMP-9使其生物可利用（Bergers，G.，R.布雷肯湾McMahon，T. H.武氏T.伊托河Tamaki，K. Tanzawa，P. Thorpe，S. Itohara，Z. Werb和D.哈纳汉2000. 2：737-744）。我们表明，VEGF是一种破骨细胞的趋化因子。此外，破骨细胞侵入肥大软骨需要VEGF，因为它被阻断VEGF功能所抑制。这些观察结果确定了MMP-9和VEGF对早期骨发育至关重要的特定作用。
Bone development requires the recruitment of osteoclast precursors from surrounding mesenchyme, thereby allowing the key events of bone growth such as marrow cavity formation, capillary invasion, and matrix remodeling. We demonstrate that mice deficient in gelatinase B/matrix metalloproteinase (MMP)-9 exhibit a delay in osteoclast recruitment. Histological analysis and specialized invasion and bone resorption models show that MMP-9 is specifically required for the invasion of osteoclasts and endothelial cells into the discontinuously mineralized hypertrophic cartilage that fills the core of the diaphysis. However, MMPs other than MMP-9 are required for the passage of the cells through unmineralized type I collagen of the nascent bone collar, and play a role in resorption of mineralized matrix. MMP-9 stimulates the solubilization of unmineralized cartilage by MMP-13, a collagenase highly expressed in hypertrophic cartilage before osteoclast invasion. Hypertrophic cartilage also expresses vascular endothelial growth factor (VEGF), which binds to extracellular matrix and is made bioavailable by MMP-9 (Bergers, G., R. Brekken, G. McMahon, T.H. Vu, T. Itoh, K. Tamaki, K. Tanzawa, P. Thorpe, S. Itohara, Z. Werb, and D. Hanahan. 2000. Nat. Cell Biol. 2:737–744). We show that VEGF is a chemoattractant for osteoclasts. Moreover, invasion of osteoclasts into the hypertrophic cartilage requires VEGF because it is inhibited by blocking VEGF function. These observations identify specific actions of MMP-9 and VEGF that are critical for early bone development.
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影响因子：
12.7
作者：
GRABER, HU;MULLER, CF;ZURBRIGGEN, A
通讯作者：
ZURBRIGGEN, A
巨噬细胞刺激因子刺激分离的破骨细胞中的存活和趋化行为。
DOI：
10.1084/jem.178.5.1733
发表时间：
1993-11-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Fuller K;Owens JM;Jagger CJ;Wilson A;Moss R;Chambers TJ
通讯作者：
Chambers TJ
影响因子：
7.4
作者：
BERGMAN, I;LOXLEY, R
通讯作者：
LOXLEY, R
影响因子：
3.5
作者：
GILLET, C;EECKHOUT, Y;VAES, G
通讯作者：
VAES, G
影响因子：
4.8
作者：
Jemtland, R;Lee, KC;Segre, GV
通讯作者：
Segre, GV