Therapeutic approaches to activate the canonical Wnt pathway for bone regeneration.
Therapeutic approaches to activate the canonical Wnt pathway for bone regeneration.
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DOI：
10.1002/term.3349
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发表时间：
2022-11
影响因子：
3.3
通讯作者：
Bahney, Chelsea
中科院分区：
文献类型：
--
作者：
Nelson, Anna Laura;Fontana, GianLuca;Miclau, Elizabeth;Rongstad, Mallory;Murphy, William;Huard, Johnny;Ehrhart, Nicole;Bahney, Chelsea
经典无翼相关整合位点（Wnt）通路的激活已被证明可增加骨形成，因此具有用于骨科疾病的治疗潜力。然而，开发实现Wnt活化的有效策略的尝试遇到了几个挑战。Wnt配体的固有疏水性使得分离和纯化蛋白质变得困难。为了规避这些挑战，许多人试图靶向Wnt信号通路的细胞外抑制剂，如Wnt信号通路抑制剂Sclerostin和Dickkopf-1，或使用小分子、离子和蛋白质来增加靶向Wnt基因。在这里，我们回顾了全身和局部生物活性方法，以增强骨形成或改善骨修复，通过基于抗体的治疗，合成Wnt替代品和支架掺杂靶向典型Wnt。最后，我们简要回顾了新兴技术，如mRNA治疗和重复的规律间隔短回文重复序列技术，这些技术是未来临床翻译的有前途的方法。
Activation of the canonical Wingless‐related integration site (Wnt) pathway has been shown to increase bone formation and therefore has therapeutic potential for use in orthopedic conditions. However, attempts at developing an effective strategy to achieve Wnt activation has been met with several challenges. The inherent hydrophobicity of Wnt ligands makes isolating and purifying the protein difficult. To circumvent these challenges, many have sought to target extracellular inhibitors of the Wnt pathway, such as Wnt signaling pathway inhibitors Sclerostin and Dickkopf‐1, or to use small molecules, ions and proteins to increase target Wnt genes. Here, we review systemic and localized bioactive approaches to enhance bone formation or improve bone repair through antibody‐based therapeutics, synthetic Wnt surrogates and scaffold doping to target canonical Wnt. We conclude with a brief review of emerging technologies, such as mRNA therapy and Clustered Regularly Interspaced Short Palindromic Repeats technology, which serve as promising approaches for future clinical translation.
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影响因子：
5.6
作者：
Gaur, Tripti;Wixted, John J.;Hussain, Sadiq;O'Connell, Shannon L.;Morgan, Elise F.;Ayers, David C.;Komm, Barry S.;Bodine, Peter V.;Stein, Gary S.;Lian, Jane B.
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影响因子：
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作者：
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通讯作者：
Alman BA
DOI：
10.1073/pnas.0505259102
发表时间：
2005-11-29
影响因子：
11.1
作者：
Clément-Lacroix, P;Ai, MR;Rawadi, G
通讯作者：
Rawadi, G
影响因子：
64.5
作者：
Batra R;Nelles DA;Pirie E;Blue SM;Marina RJ;Wang H;Chaim IA;Thomas JD;Zhang N;Nguyen V;Aigner S;Markmiller S;Xia G;Corbett KD;Swanson MS;Yeo GW
通讯作者：
Yeo GW
影响因子：
11.4
作者：
Aberle, H;Bauer, A;Kemler, R
通讯作者：
Kemler, R