Open AccessThe neurofibromatosis type I gene promotes autophagy via mTORC1 signalling pathway to enhance new bone formation after fracture
Author(s) -
Tan Qian,
Wu JiangYan,
Liu YaoXi,
Liu Kun,
Tang Jin,
Ye WeiHua,
Zhu GuangHui,
Mei HaiBo,
Yang Ge
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15767
Subject(s) - bone healing , bone resorption , autophagy , mtorc1 , bone fracture , microbiology and biotechnology , cancer research , chemistry , signal transduction , medicine , pi3k/akt/mtor pathway , biology , anatomy , apoptosis , radiology , biochemistry
Bone fracture is one of the most common injuries. Despite the high regenerative capacity of bones, failure of healing still occurs to near 10% of the patients. Herein, we aim to investigate the modulatory role of neurofibromatosis type I gene (NF1) to osteogenic differentiation of bone marrow–derived mesenchymal stem cells (BMSCs) and new bone formation after fracture in a rat model. We studied the NF1 gene expression in normal and non‐union bone fracture models. Then, we evaluated how NF1 overexpression modulated osteogenic differentiation of BMSCs, autophagy activity, mTORC1 signalling and osteoclastic bone resorption by qRT‐PCR, Western blot and immunostaining assays. Finally, we injected lentivirus‐ NF1 (Lv‐ NF1 ) to rat non‐union bone fracture model and analysed the bone formation process. The NF1 gene expression was significantly down‐regulated in non‐union bone fracture group, indicating NF1 is critical in bone healing process. In the NF1 overexpressing BMSCs, autophagy activity and osteogenic differentiation were significantly enhanced. Meanwhile, the NF1 overexpression inhibited mTORC1 signalling and osteoclastic bone resorption. In rat non‐union bone fracture model, the NF1 overexpression significantly promoted bone formation during fracture healing. In summary, we proved the NF1 gene is critical in non‐union bone healing, and NF1 overexpression promoted new bone formation after fracture by enhancing autophagy and inhibiting mTORC1 signalling. Our results may provide a novel therapeutic clue of promoting bone fracture healing.