Mesenchymal stem cells (MSCs) are multipotent stem cells that have a strong osteogenic differentiation capacity. However, the molecular mechanism underlying the osteogenic differentiation of MSCs remains largely unknown and thus hinders further development of MSC-based cell therapies for bone repair in the clinic. RSP5, also called NEDD4L (NEDD4-like E3 ubiquitin protein ligase), belongs to the HECT (homologous to E6-AP carboxyl terminus) domain-containing E3 ligase family. Nevertheless, although many studies have been conducted to elucidate the role of RSP5 in various biological processes, its effect on osteogenesis remains elusive. In this study, we demonstrated that the expression of RSP5 was elevated during the osteogenesis of MSCs and positively regulated the osteogenic capacity of MSCs by inducing K63-linked polyubiquitination and activation of the Akt pathway. Taken together, our findings suggest that RSP5 may be a promising target to improve therapeutic efficiency by using MSCs for bone regeneration and repair.

中文翻译：

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RSP5通过激活Akt的K63连锁泛素化，积极调节间充质干细胞的成骨分化。

间充质干细胞（MSC）是具有强大的成骨分化能力的多能干细胞。但是，MSC的成骨分化的分子机制仍是未知之数，因此阻碍了基于MSC的细胞疗法用于临床骨修复的进一步发展。RSP5，也称为NEDD4L（NEDD4样E3泛素蛋白连接酶），属于HECT（与E6-AP羧基末端同源）域E3连接酶家族。尽管如此，尽管已经进行了许多研究来阐明RSP5在各种生物学过程中的作用，但它对成骨的影响仍然难以捉摸。在这个研究中，我们证明了在MSC的成骨过程中，RSP5的表达升高，并通过诱导K63连接的多聚泛素化和Akt途径的激活来积极调节MSC的成骨能力。综上所述，我们的发现表明RSP5可能是通过使用MSC进行骨再生和修复来提高治疗效率的有希望的靶标。