Gene expression and distribution of connective tissue growth factor (CCN2/CTGF) during secondary ossification center formation
Gene expression and distribution of connective tissue growth factor (CCN2/CTGF) during secondary ossification center formation
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DOI：
10.1369/jhc.7a7263.2007
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发表时间：
2007-12-01
影响因子：
3.2
通讯作者：
Takigawa, Masaharu
中科院分区：
文献类型：
--
作者：
Oka, Morihiko;Kubota, Satoshi;Takigawa, Masaharu
CCN2/结缔组织生长因子（CCN2/CTGF）是间充质组织发育的关键信号调节剂。本研究调查了 CCN2/CTGF 作为小鼠胫骨骨骺次级骨化中心发育过程中支持血管生成和软骨生成的因子的定位和表达。 7日龄时软骨管形成和血管侵入启动了二次骨化中心的形成，并在14日龄时观察到骨化的开始。原位杂交显示，7日龄时CCN2/CTGF mRNA在软骨管和囊附着边缘组织区域有明显表达，14日龄时骨髓腔周围增殖的软骨细胞中也有明显表达。免疫染色显示CCN2/CTGF广泛分布在位于骨骺中心区域的表达细胞周围，软骨细胞肥大，软骨管进入肥厚块。此外，在次级骨化中心发现金属蛋白酶（MMP）9和CCN2/CTGF重叠分布。这些发现表明CCN2/CTGF参与建立骨骺血管化和重塑，最终决定发育中的骨骺软骨的次级骨化中心。
CCN2/connective tissue growth factor (CCN2/CTGF) is a critical signaling modulator of mesenchymal tissue development. This study investigated the localization and expression of CCN2/CTGF as a factor supporting angiogenesis and chondrogenesis during development of secondary ossification centers in the mouse tibial epiphysis. Formation of the secondary ossification center was initiated by cartilage canal formation and blood vessel invasion at 7 days of age, and onset of ossification was observed at 14 days. In situ hybridization showed that CCN2/CTGF mRNA was distinctively expressed in the region of the cartilage canal and capsule-attached marginal tissues at 7 days of age, and distinct expression was also observed in proliferating chondrocytes around the marrow space at 14 days of age. Immunostaining showed that CCN2/CTGF was distributed broadly around the expressed cells located in the central region of the epiphysis, where the chondrocytes become hypertrophic and the cartilage canal enters into the hypertrophic mass. Furthermore, an overlapping distribution of metal loproteinase (MMP)9 and CCN2/CTGF was found in the secondary ossification center. These findings suggest that the CCN2/CTGF is involved in establishing epiphyseal vascularization and remodeling, which eventually determines the secondary ossification center in the developing epiphysial cartilage.