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Published on: July 3, 2020
Matrix Metalloproteinase-9 Enhances Osteoclastogenesis: Insights from Transgenic Rabbit Bone Marrow Models and In
Yajie Chen1,2, Jialun Zou1, Manabu Niimi2
1Guangdong Province Key Laboratory, Southern China Institute of Large Animal Models for Biomedicine, School of Pharmacy and Food Engineering, Wuyi University, Jiangmen 529020, China.
Abstract:
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 × 109 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, * p < 0.01) while suppressing inflammatory cytokines (IL-1β, TNF-α). 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.
