Osteoclast resorption is dependent on a podosome‐rich structure called sealing zone. It tightly attaches the osteoclast to the bone creating a favourable acidic microenvironment for bone degradation. This adhesion structure needs to be stabilised by microtubules whose acetylation is maintained by down‐regulation of deacetylase HDAC6 and/or of microtubule destabilising kinase GSK3β activities. We already established that Dock5 is a guanine nucleotide exchange factor for Rac1. As a consequence, Dock5 inhibition results in a decrease of the GTPase activity associated with impaired podosome assembly into sealing zones and resorbing activity in osteoclasts. More, administration of C21, a chemical compound that directly inhibits the exchange activity of Dock5, disrupts osteoclast podosome organisation and protects mice against bone degradation in models recapitulating major osteolytic diseases.

中文翻译：

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Dock5 是破骨细胞微管动态不稳定的新调节剂

破骨细胞吸收取决于称为密封区的富含足体的结构。它将破骨细胞紧密地附着在骨骼上，为骨骼降解创造了有利的酸性微环境。这种粘附结构需要通过微管稳定，其乙酰化通过下调去乙酰化酶 HDAC6 和/或微管不稳定激酶 GSK3β 活性来维持。我们已经确定 Dock5 是 Rac1 的鸟嘌呤核苷酸交换因子。因此，Dock5 抑制导致 GTPase 活性降低，与受损的足体组装成密封区和破骨细胞的再吸收活性相关。更多地，施用 C21，一种直接抑制 Dock5 交换活性的化合物，