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Elevated oxidative stress contributes to the pathophysiological changes observed in ONFH. The lack of effective treatments besides surgical intervention highlights the importance of finding novel therapeutics. Our previous studies demonstrated that D7, a cyclic polypeptide, enhances the adhesion, expansion, and proliferation of bone marrow mesenchymal stem cells (BMSCs). Therefore, in this study, we investigated the therapeutic effects of D7 against ONFH in BMSCs and evaluated the underlying mechanisms. First, we screened for ONFH risk factors. Then, we applied D7 treatment to steroid\u2010induced ONFH (SONFH) in an in vitro model produced by dexamethasone (DEX) to further elucidate the underlying mechanisms. We found negative correlations among oxidative stress marker expression, growth differentiation factor 15 (GDF15) levels, and ONFH. Furthermore, we demonstrated that DEX inhibited the proliferation and induced apoptosis of BMSCs by suppressing GDF15\/AKT\/mammalian target of rapamycin (mTOR) signaling. D7 alleviated DEX\u2010induced BMSCs injury and restored the chondrogenic function of BMSCs by activating GDF15\/AKT\/mTOR signaling. In addition, DEX\u2010induced excessive reactive oxygen species (ROS) generation was an upstream trigger of GDF15\u2010mediated signaling, and D7 ameliorated this DEX\u2010induced redox imbalance by restoring the expression of antioxidants, including superoxide dismutase (SOD) 1, SOD2, and catalase, via regulation of GDF15 expression. In conclusion, our findings revealed the potential therapeutic effects of D7 in SONFH and showed that this protective function may be mediated via inhibition of DEX\u2010induced ROS and activation of GDF15\/AKT\/mTOR signaling, thereby providing insights into the potential applications of D7 in SONFH treatment.<\/jats:p>","DOI":"10.1155\/2022\/3182368","type":"journal-article","created":{"date-parts":[[2022,3,3]],"date-time":"2022-03-03T23:05:07Z","timestamp":1646348707000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Cyclic Polypeptide D7 Protects Bone Marrow Mesenchymal Cells and Promotes Chondrogenesis during Osteonecrosis of the Femoral Head via Growth Differentiation Factor 15\u2010Mediated Redox Signaling"],"prefix":"10.1155","volume":"2022","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8417-0661","authenticated-orcid":false,"given":"Jiazheng","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7529-6542","authenticated-orcid":false,"given":"Zichen","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2118-6735","authenticated-orcid":false,"given":"Linmao","family":"Lyu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changgong","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dianjie","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3596-3520","authenticated-orcid":false,"given":"Ziqing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9744-1595","authenticated-orcid":false,"given":"Shui","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,3,3]]},"reference":[{"key":"e_1_2_9_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2010.06.007"},{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.22313"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-004-1649-7"},{"key":"e_1_2_9_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/00003086-199701000-00005"},{"key":"e_1_2_9_5_2","first-page":"162","article-title":"Femoral artery constriction by norepinephrine is enhanced by methylprednisolone in a rat model","volume":"88","author":"Drescher W.","year":"2006","journal-title":"JBJS"},{"key":"e_1_2_9_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11999-008-0171-1"},{"key":"e_1_2_9_7_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-020-01956-5"},{"key":"e_1_2_9_8_2","doi-asserted-by":"crossref","unstructured":"SadoghiP. 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