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Updated: Jun 10, 2026

Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma
Published on: April 12, 2019
CXCR4 Facilitates Osteosarcoma Progression through MMP9-Mediated Cell Migration and Matrix Degradation
Hanyong Zhang1, Mengchang Xu1, Yan Jiang2
1Changsha Medical University Hunan Key Laboratory Of The Research And Development Of Novel Pharmaceutical PreparationsProvincial first-class applied discipline (pharmacy) Changsha China.
Purpose:
Osteosarcoma is a is a severe bone cancer type with a poor prognosis and limited therapies for metastatic. CXCR4 and MMP9 are connected to tumor dissemination and invasiveness, but their functional interaction in osteosarcoma remains unclear. We sought to elucidate the function of CXCR4 in promoting osteosarcoma cell migration and extracellular matrix breakdown by targeting MMP9.
Methods:
Osteoblasts (hFOB1.19) and osteosarcoma cells (MG-63, U2OS, 143B) were applied to examine the expression and role of CXCR4 and MMP9. Cells were transfected with CXCR4 siRNA, MMP9 siRNA, or overexpression plasmids. Functional assays including wound healing, Transwell invasion, qRT-PCR, Western blot, ELISA, and immunofluorescence were conducted. Rescue experiments were performed to validate the CXCR4-MMP9 regulatory axis.
Results:
CXCR4 and MMP9 were significantly upregulated in osteosarcoma cells compared with normal osteoblasts, with 143B cells showing the highest expression levels. CXCR4 silencing inhibited, whereas overexpression enhanced, cell migration, invasion, and matrix degradation. CXCR4 positively regulated MMP9 at transcriptional and functional levels, as illustrated by qRT-PCR, Western blot, ELISA. Overexpression of MMP9 in rescue experiments was able to partially negate the effects of CXCR4 knockdown, while MMP9 silencing attenuated the pro-invasive effects of CXCR4 overexpression. Co-localization of CXCR4 and MMP9 was confirmed by immunofluorescence staining.
Conclusion:
CXCR4 promotes osteosarcoma cell invasiveness through upregulation of MMP9. The CXCR4-MMP9 axis may represent a potential therapeutic target to limit osteosarcoma progression and metastasis.
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