期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
卷 1863, 期 11, 页码 2848-2861出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbadis.2017.07.036
关键词
Muscle atrophy; Fracture healing; Animal models; Akt; SC79
资金
- National Natural Science Foundation of China [81371960]
- Key National Basic Research Program of China [2012CB619101]
- Technology Support Project of the Science and Technology Commission of Shanghai [13441901302, 14441901000, 15411951200]
- New Cutting-Edge Technology Project of Shen Kang Hospital Development Center of Shanghai [SHDC12014124]
- Shanghai Jiao Tong University Cross Research Fund of Medical Engineering [YG2013MS57]
- Multicenter Clinical Research Project of Shanghai Jiao Tong University School of Medicine [DLY201506]
Muscle damage and disuse muscular atrophy are detrimental for fracture healing. It has been reported that the Akt signaling pathway plays a role in skeletal muscle hypertrophy and atrophy. The aim of this study was to further investigate whether promoting local muscle function through regulating Akt signaling affects fracture healing. For this purpose, we combined a rat model of short-term atrophy of the quadriceps with a femoral fracture model. In brief, botulinum toxin-A (BTX) were administered locally into the quadriceps one week before femur osteotomy to induce muscle atrophy. For the following weeks after BTX treatment, animals received injection of the Akt activator SC79 (20 mg/kg/week) or the Akt inhibitor MK2206 (100 mg/kg/week). We found that SC79 significantly accelerated the recovery of quadriceps weight and fiber size after BTX treatment. Moreover, animals that received SC79 injection showed greater bone callus volumes and superior femur mechanical properties. Immunological analysis revealed that the expression levels of the muscle-specific marker myosin heavy chain (MHC) were increased while expression of a negative regulator of muscle mass and function, myostatin, was decreased after SC79 treatment. Furthermore, SC79 increased the mRNA levels of the myogenic regulatory factors MyoD, MRF4 and Myf5 and promoted myotube formation in vitro. Taken together, these findings reveal that SC79 could accelerate the recovery of reversible muscular atrophy induced by BTX and subsequently promote fracture healing through activation of the Akt signaling pathway, which suggests its therapeutic potential in orthopedics.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据