Osteoporosis (OP) is a systemic skeletal disease leading to fragility fractures and is a major health issue globally. WNT/β-catenin signaling regulates bone-remodeling processes and plays vital roles in OP development. However, the underlying regulatory mechanisms behind WNT/β-catenin signaling in OP requires clarification, as further studies are required to identify novel alternate therapeutic agents to improve OP. Here we report that fibronectin 1 (FN-1) promoted differentiation and mineralization of osteoblasts by activating WNT/β-catenin pathway, in cultured pre-osteoblasts. With isobaric tags for relative and absolute quantitation labeling proteomics analysis, we investigated protein changes in bone samples from OP patients and normal controls. FN-1 accumulated in osteoblasts in bone samples from OP patients and age-related OP mice compared to control group. In addition, we observed that integrin β1 (ITGB1) acts as an indispensable signaling molecule for the interplay between FN-1 and β-catenin, and that FN-1 expression increased, but ITGB1 expression decreased in osteoblasts during OP progression. Therefore, our study reveals a novel explanation for WNT/β-catenin pathway inactivation in OP pathology. Supplying of FN-1 and ITGB1 may provide a potential therapeutic strategy in improving bone formation during OP.
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This work was supported by the Guangxi Key R&D Project (Guike AB18050008), Guangxi Science and Technology Program (2018GXNSFAA294116, 2018GXNSFAA138074), High-level Innovation team and Outstanding Scholars Program of Colleges and Universities in Guangxi: innovative team of basic and Clinical Comprehensive Research on Bone and Joint degenerative Diseases, Scientific Research Project of High-level talents in the affiliated Hospital of Youjiang Medical College for nationalities (R20196301 and R20196306), and Open Project of Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases.
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Yang, C., Wang, C., Zhou, J. et al. Fibronectin 1 activates WNT/β-catenin signaling to induce osteogenic differentiation via integrin β1 interaction. Lab Invest 100, 1494–1502 (2020). https://doi.org/10.1038/s41374-020-0451-2
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