Objective The purpose of this study is to investigate whether mechanical growth factor (MGF) promotes mechanical response to ligament fibroblasts in osteoarthritis knee cavity via activating transcription factor 2 (ATF-2). Results Osteoarthritis ligament fibroblasts (OA-LFs) were suffered from 12% static mechanical stretch to mimic mechanical force mediated ligament injury. Meanwhile, OA-LFs were treated with MGF before and during mechanical stretch. We observed that OA delayed LFs response to mechanical injury, while MGF pretreatment promoted cells timely feedback the mechanically stimuli by inducing cellular stress. Additionally, MGF accelerated the ligament injury repair by promoting cell migration, decreasing the MMP-2 activity, and remitting the cell deformation via ATF-2 activating in cells. Conclusions Our study shows that MGF pretreatment of OA-LFs can respond quickly to mechanical damage and repair ligament tissue by activating ATF-2. Therefore, MGF has potential as a therapeutic for OA patients.