TY - JOUR TI - Fibronectin 1 activates WNT/β-catenin signaling to induce osteogenic differentiation via integrin β1 interaction AU - Yang, Chengliang AU - Wang, Chong AU - Zhou, Jing AU - Liang, Qingyang AU - He, Feng AU - Li, Feng AU - Li, Ye AU - Chen, Jinzhong AU - Zhang, Fan AU - Han, Chao AU - Liu, Jia AU - Li, Kai AU - Tang, Yujin T2 - Laboratory Investigation AB - 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. DA - 2020/06/19/ PY - 2020 DO - 10.1038/s41374-020-0451-2 DP - www.nature.com SP - 1 EP - 9 LA - en SN - 1530-0307 UR - https://www.nature.com/articles/s41374-020-0451-2 Y2 - 2020/06/22/22:34:07 ER -