{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T09:22:25Z","timestamp":1787908945373,"version":"build-2784847793"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"name":"the Special Fund Project of Central Government Guiding Local Science and Technology Development in 2019"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Cell Biochem"],"DOI":"10.1007\/s11010-026-05635-6","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T08:40:36Z","timestamp":1784191236000},"page":"3905-3917","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["SHED-Exo delivery of miR-708-5p activates PI3K\/AKT signaling pathway to alleviate glucocorticoid-induced osteogenic inhibition in BMSCs"],"prefix":"10.1007","volume":"481","author":[{"given":"Jian","family":"Lv","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxi","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinmin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xijun","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,16]]},"reference":[{"key":"5635_CR1","first-page":"519","volume":"33","author":"P Khanchandani","year":"2024","unstructured":"Khanchandani P, Narayanan A, Naik AA, Kannan V, Pradhan SS, Srimadh Bhagavatham SK, Pulukool SK (2024) Sivaramakrishnan, \u2018Clinical Characteristics, Current Treatment Options, Potential Mechanisms, Biomarkers, and Therapeutic Targets in Avascular Necrosis of Femoral Head\u2019. Med Princ Pract 33:519\u2013536","journal-title":"Med Princ Pract"},{"key":"5635_CR2","doi-asserted-by":"publisher","DOI":"10.3346\/jkms.2021.36.e177","volume":"36","author":"JT Hines","year":"2021","unstructured":"Hines JT, Jo WL, Cui Q, Mont MA, Koo KH, Cheng EY, Goodman SB, Ha YC, Hernigou P, Jones LC, Kim SY, Sakai T, Sugano N, Yamamoto T, Lee MS, Zhao D, Drescher W, Kim TY, Lee YK, Yoon BH, Baek SH, Ando W, Kim HS, Park JW (2021) Osteonecrosis of the femoral head: an updated review of ARCO on pathogenesis, staging and treatment. J Korean Med Sci 36:e177","journal-title":"J Korean Med Sci"},{"issue":"1","key":"5635_CR3","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1038\/s41598-017-00162-3","volume":"7","author":"T Pascart","year":"2017","unstructured":"Pascart T, Falgayrac G, Migaud H, Quinchon JF, Norberciak L, Budzik JF, Paccou J, Cotten A, Penel G, Cortet B (2017) Region specific Raman spectroscopy analysis of the femoral head reveals that trabecular bone is unlikely to contribute to non-traumatic osteonecrosis. Sci Rep 7:97","journal-title":"Sci Rep"},{"key":"5635_CR4","doi-asserted-by":"publisher","first-page":"1935","DOI":"10.1038\/cdd.2015.99","volume":"22","author":"H Li","year":"2015","unstructured":"Li H, Li T, Fan J, Li T, Fan L, Wang S, Weng X, Han Q, Zhao RC (2015) Mir-216a Rescues Dexamethasone Suppression of Osteogenesis, Promotes Osteoblast Differentiation and Enhances Bone Formation, by Regulating C-Cbl-Mediated Pi3k\/Akt Pathway. Cell Death Differ 22:1935\u20131945","journal-title":"Cell Death Differ"},{"key":"5635_CR5","doi-asserted-by":"publisher","first-page":"1770","DOI":"10.1182\/blood-2015-05-643601","volume":"126","author":"SE Karol","year":"2015","unstructured":"Karol SE, Yang W, Van Driest SL, Chang TY, Kaste S, Bowton E, Basford M, Bastarache L, Roden DM, Denny JC, Larsen E, Winick N, Carroll WL, Cheng C, Pei D, Fernandez CA, Liu C, Smith C, Loh ML, Raetz EA, Hunger SP, Scheet P, Jeha S, Pui CH, Evans WE, Devidas M, Mattano LA Jr., Relling MV (2015) Genetics of glucocorticoid-associated osteonecrosis in children with acute lymphoblastic leukemia. Blood 126:1770\u20136","journal-title":"Blood"},{"key":"5635_CR6","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.tem.2017.10.010","volume":"29","author":"J Vandewalle","year":"2018","unstructured":"Vandewalle J, Luypaert A, De Bosscher K, Libert C (2018) Therapeutic Mechanisms of Glucocorticoids. Trends Endocrinol Metab 29:42\u201354","journal-title":"Trends Endocrinol Metab"},{"key":"5635_CR7","doi-asserted-by":"publisher","first-page":"583975","DOI":"10.3389\/fphar.2021.583975","volume":"12","author":"Y Zhang","year":"2021","unstructured":"Zhang Y, Ma L, Lu E, Huang W (2021) Atorvastatin Upregulates Microrna-186 and Inhibits the Tlr4-Mediated Mapks\/Nf-Kappab Pathway to Relieve Steroid-Induced Avascular Necrosis of the Femoral Head. Front Pharmacol 12:583975","journal-title":"Front Pharmacol"},{"key":"5635_CR8","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.447","volume":"11","author":"N Yang","year":"2021","unstructured":"Yang N, Sun H, Xue Y, Zhang W, Wang H, Tao H, Liang X, Li M, Xu Y, Chen L, Zhang L, Huang L, Geng D (2021) Inhibition of Magl Activates the Keap1\/Nrf2 Pathway to Attenuate Glucocorticoid-Induced Osteonecrosis of the Femoral Head. Clin Transl Med 11:e447","journal-title":"Clin Transl Med"},{"key":"5635_CR9","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.carbpol.2019.03.004","volume":"214","author":"W Huang","year":"2019","unstructured":"Huang W, Deng H, Jin S, Yang W, Wang H, Meng C, Wang H, Yang S (2019) A Polysaccharide from Dried Aerial Parts of Agrimonia Pilosa: Structural Characterization and Its Potential Therapeutic Activity for Steroid\u2013Induced Necrosis of the Femoral Head (Sanfh). Carbohydr Polym 214:71\u201379","journal-title":"Carbohydr Polym"},{"key":"5635_CR10","doi-asserted-by":"publisher","first-page":"5807","DOI":"10.1073\/pnas.0937635100","volume":"100","author":"M Miura","year":"2003","unstructured":"Miura M, Gronthos S, Zhao M, Lu B, Fisher LW, Robey PG, Shi S (2003) Shed: stem cells from human exfoliated deciduous teeth. Proc Natl Acad Sci U S A 100:5807\u201312","journal-title":"Proc Natl Acad Sci U S A"},{"key":"5635_CR11","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1177\/0963689718809090","volume":"28","author":"LV Pereira","year":"2019","unstructured":"Pereira LV, Bento RF, Cruz DB, Marchi C, Salomone R, Oiticicca J, Costa MP, Haddad LA, Mingroni-Netto RC, Costa H (2019) Stem Cells from Human Exfoliated Deciduous Teeth (Shed) Differentiate in Vivo and Promote Facial Nerve Regeneration. Cell Transpl 28:55\u201364","journal-title":"Cell Transpl"},{"key":"5635_CR12","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21113807","author":"YR Chen","year":"2020","unstructured":"Chen YR, Lai PL, Chien Y, Lee PH, Lai YH, Ma HI, Shiau CY, Wang KC (2020) Improvement of impaired motor functions by human dental exfoliated deciduous teeth stem cell-derived factors in a rat model of Parkinson\u2019s disease. Int J Mol Sci. https:\/\/doi.org\/10.3390\/ijms21113807","journal-title":"Int J Mol Sci"},{"key":"5635_CR13","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.dental.2024.10.015","volume":"41","author":"J Ding","year":"2025","unstructured":"Ding J, Sun Z, Ma L, Wang L, Liao Z, Liang L, Yang H, Mao R (2025) Microspheres of Stem Cells from Human Exfoliated Deciduous Teeth Exhibit Superior Pulp Regeneration Capacity. Dent Mater 41:70\u201380","journal-title":"Dent Mater"},{"key":"5635_CR14","doi-asserted-by":"publisher","first-page":"2694","DOI":"10.7150\/thno.31801","volume":"9","author":"X Yang","year":"2019","unstructured":"Yang X, Ma Y, Guo W, Yang B, Tian W (2019) Stem Cells from Human Exfoliated Deciduous Teeth as an Alternative Cell Source in Bio-Root Regeneration. Theranostics 9:2694\u20132711","journal-title":"Theranostics"},{"key":"5635_CR15","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1007\/s00595-019-01783-z","volume":"49","author":"T Taguchi","year":"2019","unstructured":"Taguchi T, Yanagi Y, Yoshimaru K, Zhang XY, Matsuura T, Nakayama K, Kobayashi E, Yamaza H, Nonaka K, Ohga S (2019) Yamaza, \u2018Regenerative Medicine Using Stem Cells from Human Exfoliated Deciduous Teeth (Shed): A Promising New Treatment in Pediatric Surgery\u2019. Surg Today 49:316\u2013322","journal-title":"Surg Today"},{"key":"5635_CR16","doi-asserted-by":"publisher","first-page":"237","DOI":"10.7150\/thno.21945","volume":"8","author":"C He","year":"2018","unstructured":"He C, Zheng S, Luo Y, Wang B (2018) Exosome Theranostics: Biology and Translational Medicine. Theranostics 8:237\u2013255","journal-title":"Theranostics"},{"key":"5635_CR17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.diff.2019.10.003","volume":"111","author":"M Wang","year":"2020","unstructured":"Wang M, Li J, Ye Y, He S, Song J (2020) Shed-Derived Conditioned Exosomes Enhance the Osteogenic Differentiation of Pdlscs Via Wnt and Bmp Signaling in Vitro. Differentiation 111:1\u201311","journal-title":"Differentiation"},{"key":"5635_CR18","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25168560","author":"CY Lin","year":"2024","unstructured":"Lin CY, Naruphontjirakul P, Huang TY, Wu YC, Cheng WH, Su WT (2024) The exosomes of stem cells from human exfoliated deciduous teeth suppress inflammation in osteoarthritis. Int J Mol Sci. https:\/\/doi.org\/10.3390\/ijms25168560","journal-title":"Int J Mol Sci"},{"key":"5635_CR19","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1186\/s13287-019-1341-7","volume":"10","author":"P Luo","year":"2019","unstructured":"Luo P, Jiang C, Ji P, Wang M, Xu J (2019) Exosomes of Stem Cells from Human Exfoliated Deciduous Teeth as an Anti-Inflammatory Agent in Temporomandibular Joint Chondrocytes Via Mir-100-5p\/Mtor. Stem Cell Res Ther 10:216","journal-title":"Stem Cell Res Ther"},{"key":"5635_CR20","doi-asserted-by":"publisher","first-page":"148575","DOI":"10.1016\/j.gene.2024.148575","volume":"923","author":"X Fei Liu","year":"2024","unstructured":"Fei Liu X, Wang J, Xu Y, Lu Y, Bai, Lv J (2024) Preliminary Study on the Mechanism by Which Exosomes Derived from Human Exfoliated Deciduous Teeth Improve the Proliferation and Osteogenic Inhibitory Effect of Glucocorticoid-Induced Bmscs. Gene 923:148575","journal-title":"Gene"},{"key":"5635_CR21","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1038\/nprot.2008.73","volume":"3","author":"TD Schmittgen","year":"2008","unstructured":"Schmittgen TD, Livak KJ (2008) Analyzing Real-Time Pcr Data by the Comparative C(T) Method. Nat Protoc 3:1101\u20131108","journal-title":"Nat Protoc"},{"key":"5635_CR22","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.gene.2018.05.091","volume":"671","author":"A Wang","year":"2018","unstructured":"Wang A, Ren M, Wang J (2018) The Pathogenesis of Steroid-Induced Osteonecrosis of the Femoral Head: A Systematic Review of the Literature. Gene 671:103\u2013109","journal-title":"Gene"},{"key":"5635_CR23","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1038\/s41413-023-00259-8","volume":"11","author":"F Zhang","year":"2023","unstructured":"Zhang F, Wei L, Wang L, Wang T, Xie Z, Luo H, Li F, Zhang J, Dong W, Liu G, Kang Q, Zhu X, Peng W (2023) Far591 Promotes the Pathogenesis and Progression of Sonfh by Regulating Fos Expression to Mediate the Apoptosis of Bone Microvascular Endothelial Cells. Bone Res 11:27","journal-title":"Bone Res"},{"key":"5635_CR24","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2023.116649","volume":"475","author":"Q Liu","year":"2023","unstructured":"Liu Q, Wu Y, Li S, Yoon S, Zhang J, Wang X, Hu L, Su C, Zhang C, Wu Y (2023) Ursolic acid alleviates steroid-induced avascular necrosis of the femoral head in mouse by inhibiting apoptosis and rescuing osteogenic differentiation. Toxicol Appl Pharmacol 475:116649","journal-title":"Toxicol Appl Pharmacol"},{"key":"5635_CR25","first-page":"3175","volume":"20","author":"J Ye","year":"2019","unstructured":"Ye J, Wei D, Peng L, Chang T (2019) Ginsenoside Rb1 Prevents Steroid\u2013Induced Avascular Necrosis of the Femoral Head through the Bone Morphogenetic Protein\u20132 and Vascular Endothelial Growth Factor Pathway. Mol Med Rep 20:3175\u20133181","journal-title":"Mol Med Rep"},{"key":"5635_CR26","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2019.01161","volume":"10","author":"CL Xia","year":"2019","unstructured":"Xia CL, Lyu Y, Li C, Li H, Zhang ZT, Yin SW, Mao Y, Li W, Kong LY, Liang B, Jiang HK, Li-Ling J, Liu CX, Wei J (2019) Rare de novoIGF2 variant on the paternal allele in a patient with Silver-Russell syndrome. Front Genet 10:1161","journal-title":"Front Genet"},{"key":"5635_CR27","doi-asserted-by":"publisher","first-page":"5930","DOI":"10.3390\/ijms22115930","volume":"22","author":"C Melzer","year":"2021","unstructured":"Melzer C, Ohe JV, Luo T, Hass R (2021) Spontaneous fusion of MSC with breast cancer cells can generate tumor dormancy. Int J Mol Sci 22:5930","journal-title":"Int J Mol Sci"},{"key":"5635_CR28","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1186\/s13287-020-01770-z","volume":"11","author":"PS Patrick","year":"2020","unstructured":"Patrick PS, Kolluri KK, Zaw Thin M, Edwards A, Sage EK, Sanderson T, Weil BD, Dickson JC, Lythgoe MF, Lowdell M, Janes SM, Kalber TL (2020) Lung Delivery of Mscs Expressing Anti-Cancer Protein Trail Visualised with (89)Zr-Oxine Pet-Ct. Stem Cell Res Ther 11:256","journal-title":"Stem Cell Res Ther"},{"key":"5635_CR29","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222112018","author":"JK Bar","year":"2021","unstructured":"Bar JK, Lis-Nawara A, Grelewski PG (2021) Dental pulp stem cell-derived secretome and its regenerative potential. Int J Mol Sci. https:\/\/doi.org\/10.3390\/ijms222112018","journal-title":"Int J Mol Sci"},{"key":"5635_CR30","first-page":"6551","volume":"17","author":"H Wang","year":"2018","unstructured":"Wang H, Zhong Q, Yang T, Qi Y, Fu M, Yang X, Qiao L, Ling Q, Liu S, Zhao Y (2018) Comparative Characterization of Shed and Dpscs During Extended Cultivation in Vitro. Mol Med Rep 17:6551\u20136559","journal-title":"Mol Med Rep"},{"key":"5635_CR31","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1038\/s41419-022-05034-x","volume":"13","author":"M Kou","year":"2022","unstructured":"Kou M, Huang L, Yang J, Chiang Z, Chen S, Liu J, Guo L, Zhang X, Zhou X, Xu X, Yan X, Wang Y, Zhang J, Xu A, Tse HF (2022) Lian, \u2018Mesenchymal Stem Cell-Derived Extracellular Vesicles for Immunomodulation and Regeneration: A Next Generation Therapeutic Tool?\u2018. Cell Death Dis 13:580","journal-title":"Cell Death Dis"},{"key":"5635_CR32","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1080\/08977194.2023.2227269","volume":"41","author":"Y Wang","year":"2023","unstructured":"Wang Y, Su Q, Tang H, Tian Q, Lin X, Fu M, Zhang R, Luo Z, Zhang K (2023) Microfracture Technique Combined with Mesenchymal Stem Cells Inducer Represses Mir-708-5p to Target Special at-Rich Sequence-Binding Protein 2 to Drive Cartilage Repair and Regeneration in Rabbit Knee Osteoarthritis. Growth Factors 41:115\u2013129","journal-title":"Growth Factors"},{"key":"5635_CR33","doi-asserted-by":"publisher","first-page":"3439","DOI":"10.2147\/DDDT.S177128","volume":"12","author":"J Wu","year":"2018","unstructured":"Wu J, Fan W, Ma L, Geng X (2018) Mir-708-5p Promotes Fibroblast-Like Synoviocytes\u2019 Cell Apoptosis and Ameliorates Rheumatoid Arthritis by the Inhibition of Wnt3a\/Beta-Catenin Pathway. Drug Des Devel Ther 12:3439\u20133447","journal-title":"Drug Des Devel Ther"},{"key":"5635_CR34","doi-asserted-by":"publisher","DOI":"10.3390\/vetsci9110641","author":"X Xu","year":"2022","unstructured":"Xu X, Lu H, Xu D, Yu Z, Ai N, Wang K, Li X, He J, Jiang J, Ma H, Zhang Y (2022) Mir-708-5p regulates myoblast proliferation and differentiation. Vet Sci. https:\/\/doi.org\/10.3390\/vetsci9110641","journal-title":"Vet Sci"},{"key":"5635_CR35","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.110567","volume":"130","author":"Y Hao","year":"2020","unstructured":"Hao Y, Li G (2020) Role of Efna1 in tumorigenesis and prospects for cancer therapy. Biomed Pharmacother 130:110567","journal-title":"Biomed Pharmacother"},{"key":"5635_CR36","doi-asserted-by":"publisher","first-page":"826023","DOI":"10.3389\/fcell.2022.826023","volume":"10","author":"X Xie","year":"2022","unstructured":"Xie X, Hu L, Mi B, Panayi AC, Xue H, Hu Y, Liu G, Chen L, Yan C, Zha K, Lin Z, Zhou W, Gao F, Liu G (2022) Ship1 Activator Aqx-1125 Regulates Osteogenesis and Osteoclastogenesis through Pi3k\/Akt and Nf-Kappab Signaling. Front Cell Dev Biol 10:826023","journal-title":"Front Cell Dev Biol"}],"container-title":["Molecular and Cellular Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11010-026-05635-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11010-026-05635-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11010-026-05635-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T09:15:01Z","timestamp":1787908501000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11010-026-05635-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,16]]},"references-count":36,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["5635"],"URL":"https:\/\/doi.org\/10.1007\/s11010-026-05635-6","relation":{},"ISSN":["1573-4919"],"issn-type":[{"value":"1573-4919","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,16]]},"assertion":[{"value":"19 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}}]}}