Study on the Mechanism of Hmga1 Overexpression Lentivirus Regulating Osteogenic Differentiation to Treat Osteoporosis Based on Wnt/β-catenin Pathway
10.3870/j.issn.1672-0741.24.12.022
- VernacularTitle:基于Wnt/β-catenin通路探究Hmga1过表达慢病毒调节成骨分化治疗骨质疏松症的机制
- Author:
Yue ZHANG
1
;
Zhong LI
;
Lizi YE
Author Information
1. 西南医科大学附属医院儿外科,泸州 646000;西南医科大学附属医院骨与关节外科,泸州 646000
- Publication Type:Journal Article
- Keywords:
Hmga1-overexpressing lentivirus;
osteogenic differentiation;
BMSC;
osteoporosis
- From:
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
2025;54(3):312-319
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the mechanism of high mobility group AT-hook 1(Hmga1)in regulating the osteogenic differentiation of bone marrow mesenchymal stem cell(BMSC)through the Wnt/β-catenin pathway in the treatment of osteopo-rosis.Methods Hmga1-overexpressing lentiviral vector(LV)was constructed in vitro to transfect rat BMSC,and the Wnt signal inhibitor Dickkopf-1(DKK1)was used for intervention.Osteogenic differentiation-related indices were analyzed by qRT-PCR,Western blot,alkaline phosphatase(ALP)activity detection and Alizarin red staining.Ovariectomized(OVX)osteoporosis rat model was established,and Hmga1-LV was injected into the bone marrow cavity.Micro-CT,histological staining and immuno-fluorescence techniques were used to evaluate the bone microstructure and the expression of osteogenic differentiation-related proteins.Results Hmga1 expression was upregulated in a time-dependent manner during osteogenic differentiation of BMSC,while Hmga1 expression was significantly decreased in the bone tissue of OVX rats.Overexpression of Hmga1 significantly en-hanced the ALP activity and mineralized nodule formation of BMSC,and upregulated the expression of Runt-related transcrip-tion factor 2(Runx2)and osteocalcin(Ocn).The effect was partially reversed by DKK1.Hmga1 overexpression activated the Wnt/β-catenin pathway by promoting the nuclear translocation of β-catenin.In vivo experiments showed that Hmga1-LV treat-ment significantly improved trabecular thickness(Tb.Th)and bone volume fraction(BV/TV)in OVX rats,and reduced trabecu-lar separation(Tb.Sp),but had no significant effect on osteoclast differentiation.Conclusion Hmga1 promotes BMSC osteogen-ic differentiation and reverses OVX-induced bone loss by activating the Wnt/β-catenin signaling pathway,providing a potential target for gene therapy of postmenopausal osteoporosis.
