Chen Yajie, Zou Jialun, Niimi Manabu, Qiu Xuan, Zhang Shuang, Yang Han, Zhu Maobi, Fan Jianglin
Guangdong Province Key Laboratory, Southern China Institute of Large Animal Models for Biomedicine, School of Pharmacy and Food Engineering, Wuyi University, Jiangmen 529020, China.
Department of Molecular Pathology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo 409-3898, Japan.
Int J Mol Sci. 2025 Mar 29;26(7):3194. doi: 10.3390/ijms26073194.
Osteoclastogenesis is tightly regulated by receptor activator of nuclear factor kappa-B ligand (RANKL) signaling, yet the role of matrix metalloproteinase-9 (MMP-9) in this process remains controversial. We established a high-yield osteoclastogenesis system using cryopreserved rabbit bone marrow cells (1 × 10 cells/femur) treated with Macrophage colony-stimulating factor (M-CSF) and RANKL. Bone marrow cells from MMP-9 transgenic rabbits (macrophage-specific overexpression) and MMP-9-transfected RAW264.7 macrophages were compared to wild-type controls. MMP-9 overexpression increased osteoclastogenesis 5.5-fold (20 ng/mL RANKL, * < 0.01) while suppressing inflammatory cytokines (). RAW264.7 macrophages stably transfected with human MMP-9 similarly exhibited reduced inflammatory cytokine levels and enhanced osteoclastogenesis. MMP-9 acts as a dual regulator of osteoclastogenesis and inflammation, suggesting therapeutic potential for osteoporosis management.
破骨细胞生成受核因子κB受体活化因子配体（RANKL）信号严格调控，但基质金属蛋白酶9（MMP-9）在此过程中的作用仍存在争议。我们使用经巨噬细胞集落刺激因子（M-CSF）和RANKL处理的冷冻保存兔骨髓细胞（1×10个细胞/股骨）建立了一个高产破骨细胞生成系统。将MMP-9转基因兔（巨噬细胞特异性过表达）的骨髓细胞和MMP-9转染的RAW264.7巨噬细胞与野生型对照进行比较。MMP-9过表达使破骨细胞生成增加5.5倍（20 ng/mL RANKL，*<0.01），同时抑制炎性细胞因子（）。稳定转染人MMP-9的RAW264.7巨噬细胞同样表现出炎性细胞因子水平降低和破骨细胞生成增强。MMP-9作为破骨细胞生成和炎症的双重调节因子，提示其在骨质疏松症治疗方面具有潜在应用价值。
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