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...

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Main Authors: Liu Liantao, Rong Shuai, Zhou Xiaobin, Li Hao, Zhen Kepei, Zheng Chong, Li Kewei
Format: Article
Language:English
Published: De Gruyter 2025-08-01
Series:Open Life Sciences
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Online Access:https://doi.org/10.1515/biol-2025-1126
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author Liu Liantao
Rong Shuai
Zhou Xiaobin
Li Hao
Zhen Kepei
Zheng Chong
Li Kewei
author_facet Liu Liantao
Rong Shuai
Zhou Xiaobin
Li Hao
Zhen Kepei
Zheng Chong
Li Kewei
author_sort Liu Liantao
collection DOAJ
description 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.
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spelling doaj-art-9d3ce3cdf0c448119f6566c6286af1ce2025-08-20T03:03:04ZengDe GruyterOpen Life Sciences2391-54122025-08-0120130283210.1515/biol-2025-1126SATB2 promotes humeral fracture healing in rats by activating the PI3K/AKT pathwayLiu Liantao0Rong Shuai1Zhou Xiaobin2Li Hao3Zhen Kepei4Zheng Chong5Li Kewei6Department of Pediatric Orthopedics, The Third Hospital of Shijiazhuang, No.15, South Sports Street, Chang’an District, Shijiazhuang, Hebei, 050011, ChinaDepartment of Pediatric Orthopedics, The Third Hospital of Shijiazhuang, No.15, South Sports Street, Chang’an District, Shijiazhuang, Hebei, 050011, ChinaDepartment of Trauma Orthopedics III, The Third Hospital of Shijiazhuang, Shijiazhuang, Hebei, 050011, ChinaDepartment of Pediatric Orthopedics, The Third Hospital of Shijiazhuang, No.15, South Sports Street, Chang’an District, Shijiazhuang, Hebei, 050011, ChinaDepartment of Pediatric Orthopedics, The Third Hospital of Shijiazhuang, No.15, South Sports Street, Chang’an District, Shijiazhuang, Hebei, 050011, ChinaDepartment of Pediatric Orthopedics, The Third Hospital of Shijiazhuang, No.15, South Sports Street, Chang’an District, Shijiazhuang, Hebei, 050011, ChinaDepartment of Pediatric Orthopedics, The Third Hospital of Shijiazhuang, No.15, South Sports Street, Chang’an District, Shijiazhuang, Hebei, 050011, ChinaThe 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.https://doi.org/10.1515/biol-2025-1126satb2pi3k/akthumeral fracture
spellingShingle Liu Liantao
Rong Shuai
Zhou Xiaobin
Li Hao
Zhen Kepei
Zheng Chong
Li Kewei
SATB2 promotes humeral fracture healing in rats by activating the PI3K/AKT pathway
Open Life Sciences
satb2
pi3k/akt
humeral fracture
title SATB2 promotes humeral fracture healing in rats by activating the PI3K/AKT pathway
title_full SATB2 promotes humeral fracture healing in rats by activating the PI3K/AKT pathway
title_fullStr SATB2 promotes humeral fracture healing in rats by activating the PI3K/AKT pathway
title_full_unstemmed SATB2 promotes humeral fracture healing in rats by activating the PI3K/AKT pathway
title_short SATB2 promotes humeral fracture healing in rats by activating the PI3K/AKT pathway
title_sort satb2 promotes humeral fracture healing in rats by activating the pi3k akt pathway
topic satb2
pi3k/akt
humeral fracture
url https://doi.org/10.1515/biol-2025-1126
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AT zhouxiaobin satb2promoteshumeralfracturehealinginratsbyactivatingthepi3kaktpathway
AT lihao satb2promoteshumeralfracturehealinginratsbyactivatingthepi3kaktpathway
AT zhenkepei satb2promoteshumeralfracturehealinginratsbyactivatingthepi3kaktpathway
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