Functional role of hedgehog pathway in osteoarthritis
Functional role of hedgehog pathway in osteoarthritis
复制标题
Hedgehog通路在骨关节炎中的功能作用
DOI：
10.1002/cbf.3448
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发表时间：
2019-12
影响因子：
3.6
通讯作者：
Miao He
中科院分区：
文献类型：
--
作者：
Wenfeng Xiao;Yusheng Li;Ang Deng;Yuntao Yang;Miao He
hedgehog信号通路是后生动物发育的关键调控因子之一，在多种发育和生理过程中起着重要的调控作用。但它在许多人类疾病中被异常激活，包括骨关节炎（OA）。在这项研究中，我们回顾了刺猬信号通路在OA的发展和进展中的关联，并评估了针对该通路预防OA的努力。通常在OA中，hedgehog的激活诱导肥大标志物（包括X型胶原蛋白）表达上调，增加一氧化氮和前列腺素E2的产生，几种基质降解酶（包括基质金属蛋白酶和人膝关节软骨中具有血小板反应蛋白基序的去整合素和金属蛋白酶）的产生，导致软骨变性，从而导致OA。靶向hedgehog信号传导可能是预防或治疗OA的可行策略。hedgehog信号传导的化学抑制剂很有前途，但它们会引起严重的副作用。HH基因的敲除不是人类OA治疗的一种选择，因为不可能在较大动物中删除HH。在未来利用大型动物OA模型的研究中，通过局部递送小干扰RNA实现HH的有效敲低可能是预防OA的更有效方法。然而，由于软骨和软骨下骨具有不同的生理功能，开发单一的支架仍然是一个主要的问题。有必要进行更多的研究，以确定在临床条件下有效靶向刺猬途径的选择性抑制剂。
The hedgehog signalling pathway is one of the key regulators of metazoan development, and it plays an important role in the regulation of a variety of developmental and physiological processes. But it is aberrantly activated in many human diseases, including osteoarthritis (OA). In this study, we have reviewed the association of hedgehog signalling pathway in the development and progression of OA and evaluated the efforts to target this pathway for the prevention of OA. Usually in OA, activation of hedgehog induces up‐regulation of the expression of hypertrophic markers, including type X collagen, increases production of nitric oxide and prostaglandin E2, several matrix‐degrading enzymes including matrix metalloproteinase and a disintegrin and metalloproteinase with thrombospondin motifs in human knee joint cartilage leading to cartilage degeneration, and thus contributes in OA. Targeting hedgehog signalling might be a viable strategy to prevent or treat OA. Chemical inhibitors of hedgehog signalling is promising, but they cause severe side effects. Knockdown of HH gene is not an option for OA treatment in humans because it is not possible to delete HH in larger animals. Efficient knockdown of HH achieved by local delivery of small interfering RNA in future studies utilizing large animal OA models might be a more efficient approach for the prevention of OA. However, it remains a major problem to develop one single scaffold due to the different physiological functions of cartilage and subchondral bones possess. More studies are necessary to identify selective inhibitors for efficiently targeting the hedgehog pathway in clinical conditions.
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影响因子：
7
作者：
Thompson CL;Chapple JP;Knight MM
通讯作者：
Knight MM
敲低印度刺猬蛋白会诱导成骨细胞MC3T3 − E1细胞的细胞生长和分化的抑制作用。
影响因子：
3.4
作者：
Deng A;Zhang H;Hu M;Liu S;Gao Q;Wang Y;Guo C
通讯作者：
Guo C
影响因子：
3.5
作者：
Olex AL;Turkett WH;Fetrow JS;Loeser RF
通讯作者：
Loeser RF
影响因子：
5.2
作者：
Huang SY;Yang JY
通讯作者：
Yang JY
DOI：
--
发表时间：
2005-05
期刊：
The Journal of rheumatology
影响因子：
--
作者：
E. Tchetina;Ginette Squires;A. Poole
通讯作者：
E. Tchetina;Ginette Squires;A. Poole