Ohba Shinsuke
Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
J Dev Biol. 2016 Jun 3;4(2):20. doi: 10.3390/jdb4020020.
Hedgehog (Hh) signaling plays crucial roles in the patterning and morphogenesis of various organs within the bodies of vertebrates and insects. Endochondral ossification is one of the notable developmental events in which Hh signaling acts as a master regulator. Among three Hh proteins in mammals, Indian hedgehog (Ihh) is known to work as a major Hh input that induces biological impact of Hh signaling on the endochondral ossification. Ihh is expressed in prehypertrophic and hypertrophic chondrocytes of developing endochondral bones. Genetic studies so far have demonstrated that the Ihh-mediated activation of Hh signaling synchronizes chondrogenesis and osteogenesis during endochondral ossification by regulating the following processes: (1) chondrocyte differentiation; (2) chondrocyte proliferation; and (3) specification of bone-forming osteoblasts. Ihh not only forms a negative feedback loop with parathyroid hormone-related protein (PTHrP) to maintain the growth plate length, but also directly promotes chondrocyte propagation. Ihh input is required for the specification of progenitors into osteoblast precursors. The combinatorial approaches of genome-wide analyses and mouse genetics will facilitate understanding of the regulatory mechanisms underlying the roles of Hh signaling in endochondral ossification, providing genome-level evidence of the potential of Hh signaling for the treatment of skeletal disorders.
刺猬信号通路（Hh）在脊椎动物和昆虫体内各种器官的模式形成和形态发生过程中发挥着关键作用。软骨内成骨是刺猬信号通路作为主要调节因子发挥作用的显著发育事件之一。在哺乳动物的三种刺猬蛋白中，印度刺猬蛋白（Ihh）被认为是刺猬信号通路对软骨内成骨产生生物学影响的主要输入信号。Ihh在发育中的软骨内骨的前肥大和肥大软骨细胞中表达。迄今为止的遗传学研究表明，Ihh介导的刺猬信号通路激活通过调节以下过程，在软骨内成骨过程中使软骨生成和成骨同步：（1）软骨细胞分化；（2）软骨细胞增殖；（3）骨形成成骨细胞的特化。Ihh不仅与甲状旁腺激素相关蛋白（PTHrP）形成负反馈回路以维持生长板长度，还直接促进软骨细胞增殖。Ihh信号输入是祖细胞分化为成骨细胞前体所必需的。全基因组分析和小鼠遗传学的综合方法将有助于理解刺猬信号通路在软骨内成骨中作用的调控机制，为刺猬信号通路治疗骨骼疾病的潜力提供基因组水平的证据。
