Abstract
Approximately 10–15% of all bone fractures do not heal properly, causing patient morbidity and additional medical care expenses. Therefore, better mechanism-based fracture repair approaches are needed. In this study, a reduced number of osteoclasts (OCs) and autophagosomes/autolysosomes in OC can be observed in GPCR kinase 2-interacting protein 1 (GIT1) knockout (KO) mice on days 21 and 28 post-fracture, compared with GIT1 wild-type (GIT1 WT) mice. Furthermore, in vitro experiments revealed that GIT1 contributes to OC autophagy under starvation conditions. Mechanistically, GIT1 interacted with Beclin1 and promoted Beclin1 phosphorylation at Thr119, which induced the disruption of Beclin1 and Bcl2 binding under starvation conditions, thereby, positively regulating autophagy. Taken together, the findings suggest a previously unappreciated role of GIT1 in autophagy of OCs during fracture repair. Targeting GIT1 may be a potential therapeutic approach for bone fractures.
Highlights
Introduction15 million fractures occur in the United
15 million fractures occur in the UnitedStates annually due to car accidents, sports injuries, or work accidents[1]
To further investigate the association between GPCR kinase 2-interacting protein 1 (GIT1) and autophagy of OCs, we compared the number of autophagosomes and/or autolysosomes in GIT1 wild-type (GIT1 wild- type (WT)) and GIT1 KO mice under basal or fracture healing conditions
Summary
15 million fractures occur in the United. States annually due to car accidents, sports injuries, or work accidents[1]. A significant proportion (10–15%) failed to heal properly, increasing socioeconomic burdens[2,3]. There has been slow progress in the treatment for fractures in the recent years. Fracture healing is complex and involves a variety of cells and factors, which in turn, participate in the sequential, dynamic, and intricate events of osteogenesis[4,5]. Osteoclasts (OCs) are specialized bone-resorbing cells that are abundant in the fracture callus and irreplaceable in the replacement of cartilage by woven bone[6,7,8]. The spatial and temporal regulation of OCs during bone healing is poorly understood. Providing mechanism-based explanations for the healing process is expected to positively impact health
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