title: SATB2-Nanog axis links age-related intrinsic changes of mesenchymal stem cells from craniofacial bone.
abstract: Bone mesenchymal stem cells (BMSCs) senescence contributes to age-related bone loss. The alveolar bone in jaws originates from neural crest cells and possesses significant site- and age-related properties. However, such intrinsic characteristics of BMSCs from alveolar bone (AB-BMSCs) and the underlying regulatory mechanisms still remain unknown. Here, we found that the expression of special AT-rich binding protein 2 (SATB2) in human AB-BMSCs significantly decreased with aging. SATB2 knockdown on AB-BMSCs from young donors displayed these aging-related phenotypes in vitro. Meanwhile, enforced SATB2 overexpression could rejuvenate AB-BMSCs from older donors. Importantly, satb2 gene- modified BMSCs therapy could prevent the alveolar bone loss during the aging of rats. Mechanistically, the stemness regulator Nanog was identified as the direct transcriptional target of SATB2 in BMSCs and functioned as a downstream mediator of SATB2. Collectively, our data reveal that SATB2 in AB-BMSCs associates with their age-related properties, and prevents AB-BMSCs senescence via maintaining Nanog expression. These findings highlight the translational potential of transcriptional factor-based cellular reprogramming for anti-aging therapy.
authors.affiliation: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, 210029 Nanjing, China.
authors.forename: Peipei
authors.initials: P
authors.lastname: Zhou
authors.affiliation: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, 210029 Nanjing, China.
authors.forename: Geng
authors.initials: G
authors.lastname: Wu
authors.affiliation: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, 210029 Nanjing, China.|Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, 210029 Nanjing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, 210029 Nanjing, China.
authors.forename: Rongyao
authors.initials: R
authors.lastname: Xu
authors.affiliation: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, 210029 Nanjing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ge
authors.affiliation: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, 210029 Nanjing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, 210029 Nanjing, China.|Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, 210029 Nanjing, China.
authors.forename: Yuchao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, 210029 Nanjing, China.|Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, 210029 Nanjing, China.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Du
authors.affiliation: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, 210029 Nanjing, China.|Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, 210029 Nanjing, China.
authors.forename: Jinhai
authors.initials: J
authors.lastname: Ye
authors.affiliation: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, 210029 Nanjing, China.|Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, 210029 Nanjing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, 210029 Nanjing, China.|Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, 210029 Nanjing, China.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Jiang
mesh_terms: D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000818:Animals; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D036961:Matrix Attachment Region Binding Proteins / Q000235:genetics / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D000071317:Nanog Homeobox Protein / Q000235:genetics / Q000378:metabolism*; D010012:Osteogenesis / Q000502:physiology*; D051381:Rats; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D036961:Matrix Attachment Region Binding Proteins; D000071317:Nanog Homeobox Protein; C521297:SATB2 protein, human; D014157:Transcription Factors
keywords: aging; bone loss; bone mesenchymal stem cells; cytotherapy; pluripotency