Impaired vascular invasion of Cbfa1-deficient cartilage engrafted in the spleen
Impaired vascular invasion of Cbfa1-deficient cartilage engrafted in the spleen
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DOI：
10.1359/jbmr.2002.17.7.1297
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发表时间：
2002-07-01
影响因子：
6.2
通讯作者：
Komori, T
中科院分区：
文献类型：
--
作者：
Himeno, M;Enomoto, H;Komori, T
软骨细胞的成熟和血管侵入软骨是软骨内骨化过程中必不可少的。Cbfa 1-缺陷（Cbfa 1（-/-））小鼠显示成骨细胞和破骨细胞成熟的完全缺乏，以及严重抑制软骨细胞的成熟在骨骼的大部分地区。虽然软骨细胞的成熟和矿化观察到的限制领域的Cbfa 1（-/-）小鼠骨骼，血管入侵的钙化软骨从未注意到。为了探讨Cbfa 1（-/-）软骨中软骨细胞成熟和血管侵袭的可能性以及造血系统在血管侵袭过程中的作用，我们将由未成熟软骨细胞组成的胚胎18.5天（E18.5）Cbfa 1（-/-）股骨移植到正常小鼠脾脏中。一周后，移植的股骨含有表达骨桥蛋白、骨唾液酸蛋白（BSP）和基质金属蛋白酶（MMP）13的终末分化软骨细胞。在移植物骨干中，软骨基质矿化，血管和破骨细胞侵入软骨。然而，软骨细胞的成熟和血管的侵袭严重滞后相比，移植E14.5野生型股骨，其中软骨迅速被骨取代，既没有成熟的成骨细胞，也没有观察到骨形成。在原代培养的Cbfa 1（-/-）软骨细胞中，转化生长因子（TGF）β 1、血小板衍生生长因子（PDGF）、白细胞介素（IL）-1 β和甲状腺激素（T3）诱导骨桥蛋白和MMP-13表达。这些研究结果表明，造血系统中的因子能够支持不依赖于Cbfa 1的软骨血管侵袭，但没有Cbfa 1则不那么有效，这表明Cbfa 1在生长板血管化过程中与骨髓因子合作发挥作用。
Chondrocyte maturation and vascular invasion of cartilage are essential in the process of endochondral ossification. Cbfa1-deficient (Cbfa1(-/-)) mice displayed a complete absence of osteoblast and osteoclast maturation as well as severely inhibited chondrocyte maturation in most parts of the skeleton. Although chondrocyte maturation and mineralization were observed in restricted areas of Cbfa1(-/-) mouse skeleton, vascular invasion of calcified cartilage was never noted. To investigate the possibility of chondrocyte maturation and vascular invasion in Cbfa1(-/-) cartilage and the role of the hematopoietic system in the process of vascular invasion, we transplanted embryonic day 18.5 (E18.5) Cbfa1(-/-) femurs, which are composed of immature chondrocytes, into spleens of normal mice. One week later, the transplanted femurs contained terminally differentiated chondrocytes expressing osteopontin, bone sialoprotein (BSP), and matrix metalloproteinase (MMP) 13. In the diaphyses of the transplants, the cartilage matrix was mineralized and the cartilage was invaded by vascular vessels and osteoclasts. However, chondrocyte maturation and vascular invasion were severely retarded in comparison with transplants of E14.5 wild-type femurs, in which the cartilage was rapidly replaced by bone, and neither mature osteoblasts nor bone formation were observed. In primary culture of Cbfa1(-/-) chondrocytes, transforming growth factor (TGF) beta1, platelet-derived growth factor (PDGF), interleukin (IL)-1beta, and thyroid hormone (T3) induced osteopontin and MMP-13 expression. These findings indicated that factors in the hematopoietic system are able to support vascular invasion of cartilage independent of Cbfa1 but are less effective without it, suggesting that Cbfa1 functions in cooperation with factors from bone marrow in the process of growth plate vascularization.