Vacuolar protein sorting 4B is a novel regulator of osteoblast and adipocyte differentiation by activating autophagy signaling.

Vacuolar protein sorting 4B (VPS4B) is part of the endosomal sorting complex required for the transport machinery and is essential for autophagosome completion. Vps4b mutation might reduce the ability of dental follicle cells to differentiate during the mineralization process. However, the role of VPS4B in osteogenic and adipogenic differentiation from mesenchymal stem/progenitor cells remains to be explored. In the present study, we observed a substantial presence of VPS4B in bone, as well as an increase in its expression levels during the osteogenic and adipogenic differentiation of mesenchymal progenitor cells. Functional experiments revealed that VPS4B facilitated the differentiation of both osteoblasts and adipocytes. Further mechanistic investigations revealed that VPS4B was involved in autophagy in mesenchymal progenitor cells and the positive influence of VPS4B on osteogenic and adipogenic differentiation was mitigated in the context of autophagy inhibition, indicating that the pro-osteogenic and pro-adipogenic effects of VPS4B are dependent on the autophagy signaling pathway. Our research suggests that sustaining VPS4B expression at an optimal level may be advantageous for the maintenance of bone and fat homeostasis.