SATB2 promotes humeral fracture healing in rats by activating the PI3K/AKT pathway

The purpose of this study was to explore the potential mechanism of SATB2 and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway promoting fracture healing in vivo. An SD model of humeral fracture in rats was established and treated. Following a 6-week treatment period, the morphology of the fracture was assessed. Serum interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), osteocalcin, C-telopeptide of type I collagen (CTX-I), and bone morphogenetic protein 2 (BMP-2) were determined. Alkaline phosphatase (ALP), receptor activator of nuclear factor-kappa B ligand (RANKL), osteoprotegerin (OPG), and other relevant molecules such as PI3K and p-AKT were measured. The results showed that SATB2 overexpression repaired humeral fracture and bone continuity. SATB2 overexpression resulted in a significant reduction in RANKL, IL-6, TNF-α, and CTX-I expression, while simultaneously increasing OPG, ALP, osteocalcin, and BMP-2. This indicates that SATB2 inhibits osteoclast activity and promotes osteoblast function. Additionally, SATB2 overexpression increased PI3K and p-AKT protein expression in humerus. Furthermore, the inhibitory effect of the PI3K/AKT inhibitor on PI3K and p-AKT protein expression was counterbalanced by upregulating SATB2. In conclusion, SATB2 promotes fracture healing in humeral fracture rats by stimulating the proliferation and differentiation of osteoblasts, which is related to the activation of PI3K/AKT signaling pathway.