Age-dependent effects of hedgehog protein on chondrocytes
Age-dependent effects of hedgehog protein on chondrocytes
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DOI：
10.1302/0301-620x.81b6.8851
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发表时间：
1999-11-01
影响因子：
--
通讯作者：
Le, AX
中科院分区：
文献类型：
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作者：
Iwasaki, M;Jikko, A;Le, AX
骨形态发生蛋白 (BMP) 在骨形成的骨软骨发生以及骨折修复中起着至关重要的作用，刺猬蛋白和 BMP 之间的相互作用是从最近的分子研究中推断出来的。 Hedgehog 基因编码介导骨骼发育过程中的模式形成和生长的分泌蛋白。我们已经证明，印度刺猬基因 (Ihh) 在软骨原基中表达，随后在成熟和肥大的软骨细胞中表达。这一发现表明 Ihh 可能调节软骨细胞的发育。我们在这项研究中的结果表明，Ihh 转录本在小鼠的肥大软骨细胞中表达，在三天而不是三周时表达，尽管 α 的表达模式相似两种软骨中均可观察到1(X)胶原蛋白，为了探讨Ihh在软骨细胞中是否存在直接且年龄依赖性功能的可能性，用可功能性替代Ihh蛋白的Sonic Hedgehog蛋白氨基末端片段(Shh-N)处理培养的软骨细胞，Shh-N不影响三龄小鼠软骨细胞的增殖和分化，但对三日龄小鼠软骨细胞有显着影响，促进增殖。高达对照培养物的 128%，且呈剂量依赖性。尽管在经过 Shh-N 处理的培养物中没有影响，但 Shh-N 增强了甲状旁腺激素 (PTH) 对蛋白聚糖合成的刺激作用。由于Shh-N在该培养系统中对软骨细胞分化的影响不同于骨形态发生蛋白2（BMP2）和PTN，在蛋白聚糖合成和ALPase活性方面，BMP2或PTH/PTH相关蛋白不太可能介导Ihh在软骨细胞中的直接作用，我们的研究表明Ihh可以以直接且年龄依赖性的方式在软骨细胞中发挥作用。
Bone morphogenetic protein (BMP) has a crucial role in osteochondrogenesis of bone formation as well as in the repair of fractures, The interaction between hedgehog protein and BMPs is inferred from recent molecular studies. Hedgehog genes encode secreted proteins which mediate patterning and growth during skeletal development, We have shown that Indian hedgehog gene (Ihh) is expressed in cartilage anlage and later in mature and hypertrophic chondrocytes, This finding suggests that Ihh may regulate the development of chondrocytes.Our results in this study have shown that Ihh transcripts were expressed in hypertrophic chondrocytes in mice at three days but not at three weeks, although a similar expression pattern of alpha 1 (X) collagen could be observed in both types of cartilage, To investigate the possibility that there are direct and age-dependent functions of Ihh in chondrocytes, cultured chondrocytes were treated with the amino-terminal fragment of Sonic hedgehog protein (Shh-N) which can functionally substitute for Ihh protein, Shh-N did not affect the proliferation and differentiation of chondrocytes from three-meek-old mice but had a significant effect on three-day-old mice, It enhanced proliferation up to 128% of the control culture in a dose-dependent manner, Although there was no effect in Shh-N-treated cultures, Shh-N enhanced the stimulatory effect of parathyroid hormone (PTH) on the synthesis of proteoglycans. Because the effects of Shh-N on chondrocyte differentiation in this culture system differed from those of bone morphogenetic protein-2 (BMP2) and PTN, in terms of proteoglycan synthesis and ALPase activity, it is unlikely that BMP2 or PTH/PTH-related protein mediates the direct effects of Ihh in chondrocytes, Our study shows that Ihh can function in chondrocytes in a direct and age-dependent fashion.