Platelet-Derived Apoptotic Vesicles Promote Bone Regeneration via Golgi Phosphoprotein 2 (GOLPH2)-AKT Signaling Axis

Apoptotic vesicles (apoVs) are apoptotic-cell-derived
nanosized
vesicles that take on dominant roles in regulating bone homeostasis.
We have demonstrated that mesenchymal stem cell (MSC)-derived apoVs
are promising therapeutic agents for bone regeneration. However, clinical
translation of MSC-derived apoVs has been hindered due to cell expansion
and nuclear substance. As another appealing source for apoV therapy,
blood cells could potentially eliminate these limitations. However,
whether blood cells can release apoVs during apoptosis is uncertain,
and the detailed characteristics and biological properties of respective
apoVs are not elucidated. In this study, we showed that platelets
(PLTs) could rapidly release abundant apoVs during apoptosis in a
short time. To recognize the different protein expressions between
PLT-derived apoVs and PLTs, we established their precise protein landscape.
Furthermore, we identified six proteins specifically enriched in PLT-derived
apoVs, which could be considered as specific biomarkers. More importantly,
PLT-derived apoVs promoted osteogenesis of MSCs and rescued bone loss
via Golgi phosphoprotein 2 (GOLPH2)-induced AKT phosphorylation, therefore,
leading to the emergence of their potential in bone regeneration.
In summary, we comprehensively determined characteristics of PLT-derived
apoVs and confirmed their roles in bone metabolism through previously
unrecognized GOPLH2-dependent AKT signaling, providing more understanding
for exploring apoV-based therapy in bone tissue engineering.