Contributions of matrix metalloproteinases toward Meckel's cartilage resorption in mice: immunohistochemical studies, including comparisons with developing endochondral bones
Contributions of matrix metalloproteinases toward Meckel's cartilage resorption in mice: immunohistochemical studies, including comparisons with developing endochondral bones
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DOI：
10.1007/s00441-006-0329-7
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发表时间：
2007-04-01
影响因子：
3.6
通讯作者：
Yajima, Toshihiko
中科院分区：
文献类型：
--
作者：
Sakakura, Yasunori;Hosokawa, Yoichiro;Yajima, Toshihiko
梅克尔软骨的中间部分（以独特的命运消失的四个部分之一）通过软骨细胞的肥大和细胞死亡以及通过破软骨细胞对软骨的再吸收而降解。我们已经研究了免疫定位的基质金属蛋白酶-2（MMP-2），MMP-9，MMP-13和MMP-14（MMP激活级联的成员）和半乳糖凝集素-3（MMP-9的内源性底物和抗凋亡因子）在胚胎小鼠的Meckel软骨的再吸收过程中，并比较了结果与发展中的软骨内骨在后肢。MMP免疫反应性，除了MMP-2，是目前在几乎所有的软骨细胞中的中间部分Meckel的软骨。在胚胎第15天（E15），微弱的MMP-2-免疫反应和强烈的MMP-13-免疫反应信号发生在骨膜成骨细胞沉积在侧表面的骨膜骨基质中，而MMP-9和MMP-14免疫定位在Meckel软骨的外周软骨细胞中。因此，通过细胞之间的面对面的串扰的MMP的激活级联反应可能有助于Meckel软骨降解的开始。在E16，MMP-13的免疫阳性信号是可检测的皱边的破软骨细胞在吸收前线，而免疫染色半乳糖凝集素-3存在于软骨细胞分化的所有阶段，特别是在肥大的软骨细胞邻近的破软骨细胞。因此，半乳糖凝集素-3阳性肥大软骨细胞可能通过与破软骨细胞的细胞间接触来协调钙化软骨的再吸收。在E16的跖骨样本中，在成骨细胞、年轻骨细胞和骨膜骨基质中检测到MMP，而在年轻的骨膜骨细胞中半乳凝素-3免疫反应性较强。此外，强烈的MMP-9和MMP-14的免疫染色已被优先发现在前肥大的软骨细胞，虽然半乳糖凝集素-3免疫反应性显着减少肥大的软骨细胞。这些结果表明，Meckel软骨的降解涉及MMPs的激活级联反应，其不同于软骨内骨形成。
The middle portion of Meckel's cartilage (one of four portions that disappear with unique fate) degrades via hypertrophy and the cell death of chondrocytes and via the resorption of cartilage by chondroclasts. We have examined the immunolocalization of matrix metalloproteinase-2 (MMP-2), MMP-9, MMP-13, and MMP-14 (members of the MMP activation cascade) and galectin-3 (an endogenous substrate for MMP-9 and an anti-apoptotic factor) during resorption of Meckel's cartilage in embryonic mice and have compared the results with those of developing endochondral bones in hind limbs. MMP immunoreactivity, except for MMP-2, is present in nearly all chondrocytes in the middle portion of Meckel's cartilage. On embryonic day 15 (E15), faint MMP-2-immunoreactive and intense MMP13-immunoreactive signals occur in the periosteal bone matrix deposited by periosteal osteoblasts on the lateral surface, whereas MMP-9 and MMP-14 are immunolocalized in the peripheral chondrocytes of Meckel's cartilage. The activation cascade of MMPs by face-to-face cross-talk between cells may thus contribute to the initiation of Meckel's cartilage degradation. On E16, immunopositive signaling for MMP-13 is detectable in the ruffled border of chondroclasts at the resorption front, whereas immunostaining for galectin-3 is present at all stages of chondrocyte differentiation, especially in hypertrophic chondrocytes adjacent to chondroclasts. Galectin-3-positive hypertrophic chondrocytes may therefore coordinate the resorption of calcified cartilage through cell-to-cell contact with chondroclasts. In metatarsal specimens from E16, MMPs are detected in osteoblasts, young osteocytes, and the bone matrix of the periosteal envelope, whereas galectin-3 immunoreactivity is intense in young periosteal osteocytes. In addition, intense MMP-9 and MMP-14 immunostaining has been preferentially found in pre-hypertrophic chondrocytes, although galectin-3 immunoreactivity markedly decreases in hypertrophic chondrocytes. These results indicate that the degradation of Meckel's cartilage involves an activation cascade of MMPs that differs from that in endochondral bone formation.