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首页> 外文期刊>Journal of orthopaedic research >Don't hedge your bets: hedgehog signaling as a central mediator of endochondral bone development and cartilage diseases.
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Don't hedge your bets: hedgehog signaling as a central mediator of endochondral bone development and cartilage diseases.

机译:不要对冲您的赌注:刺猬信号是软骨内骨骼发育和软骨疾病的主要介质。

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摘要

Cell differentiation and patterning are vital processes in the development of the appendicular skeleton. The hedgehog (Hh) signaling pathway plays a central role in regulating the anterior-posterior axis of the distal limb as well as the length of endochondral bones. Ligand-induced Hh signaling inhibits the processing of the Gli transcription factors from activator to repressor isoforms. In the growth plate, Indian hedgehog inhibits Gli processing, resulting in accumulation of Gli activators that induce chondrocyte maturation and hypertrophic differentiation. Parathyroid hormone-like hormone promote and Gli processing to repressor forms, thus regulating the rate of hypertrophic differentiation. In cartilage diseases such as osteoarthritis and cartilage tumors, there is a recapitulation of developmental processes that involve increased Hh signaling. Studies have shown that pharmacological inhibitors of Hh signaling can attenuate the progression osteoarthritis and cartilage tumor growth. Thus, Hh blockade can serve as a potential therapy for the treatment of various cartilage diseases.
机译:细胞分化和模式化是阑尾骨骼发育中的重要过程。刺猬(Hh)信号通路在调节远端肢体的前后轴以及软骨内骨骼的长度方面起着核心作用。配体诱导的Hh信号抑制了Gli转录因子从激活物到阻遏物亚型的加工。在生长板中,印度刺猬抑制Gli加工,导致Gli激活剂积聚,从而诱导软骨细胞成熟和肥大分化。甲状旁腺激素样激素促进和Gli加工成阻遏物形式,从而调节肥大分化的速率。在诸如骨关节炎和软骨肿瘤之类的软骨疾病中,存在涉及Hh信号增强的发育过程的概括。研究表明,Hh信号的药理抑制剂可以减轻骨关节炎和软骨肿瘤生长的进程。因此,Hh阻断可作为治疗各种软骨疾病的潜在疗法。

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