Osteoclasts are multinuclear cells which maintain bone homeostasis by resorbing bone. During bone resorption, osteoclasts attach to the bone matrix via a sealing zone formed by an actin ring. Rous sarcoma oncogene (Src) is essential for actin ring formation and bone resorption. Recently, we demonstrated that plectin, a cytolinker protein, is a Src-binding protein in osteoclasts. However, the function of plectin in osteoclasts remains unknown. In this study, we demonstrated that shRNA knockdown of plectin in RAW 264.7 cells resulted in tartrate resistant acid phosphatase positive multinuclear cells (TRAP (+) MNCs) with impaired actin ring formation and bone resorption activity. Moreover, we found that in plectin-silenced TRAP (+) MNCs, Src and protein tyrosine kinase 2 beta (Pyk2), two critical kinases in osteoclastic bone resorption, were inactivated and microtubule polarity was disturbed. These results suggest that plectin plays a critical role in osteoclast biology by acting as a scaffold to facilitate Src and Pyk2 activation during microtubule organization.

中文翻译：

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Plectin 通过充当 Src 和 Pyk2 的支架在破骨细胞骨吸收过程中稳定微管

破骨细胞是多核细胞，通过吸收骨来维持骨稳态。在骨吸收过程中，破骨细胞通过肌动蛋白环形成的密封区附着在骨基质上。劳斯肉瘤癌基因 (Src) 对肌动蛋白环的形成和骨吸收至关重要。最近，我们证明了 plectin，一种细胞连接蛋白，是破骨细胞中的 Src 结合蛋白。然而，plectin 在破骨细胞中的功能仍然未知。在这项研究中，我们证明了 RAW 264.7 细胞中 plectin 的 shRNA 敲低导致了抗酒石酸酸性磷酸酶阳性多核细胞（TRAP (+) MNCs），其肌动蛋白环形成和骨吸收活性受损。此外，我们发现在 plectin 沉默的 TRAP (+) MNCs、Src 和蛋白酪氨酸激酶 2 beta (Pyk2) 中，破骨细胞骨吸收中的两种关键激酶，被灭活，微管极性被扰乱。这些结果表明 plectin 在破骨细胞生物学中起着关键作用，它作为支架在微管组织过程中促进 Src 和 Pyk2 的激活。