Transplantation of osteoporotic bone marrow stromal cells rejuvenated by the overexpression of SATB2 prevents alveolar bone loss in ovariectomized rats.
Estrogen-deficient osteoporosis is an aging-related disease with high morbidity that not only significantly increases a woman's risk of fragility fracture but is also associated with tooth and bone loss in the supporting alveolar bone of the jaw. Emerging evidence suggests that the aging of bone marrow stromal cells (BMSCs) contributes to the development of osteoporosis. In this study, we aimed to investigate the role of the special AT-rich sequence-binding protein 2 (SATB2), a stemness and senescence regulator of craniofacial BMSCs, in rat ovariectomy-induced alveolar osteoporosis. We also sought to determine whether transplantation of SATB2-modified BMSCs could ameliorate estrogen deficient alveolar bone loss. Our data revealed that BMSCs from ovariectomy-induced alveolar bone exhibited typical senescence phenotypes such as diminished stemness and osteogenic capacity, increased expression of senescence or osteoclastic markers and enhanced adipogenic potential. These phenotypic changes are a result of SATB2-mediated senescence dysregulation as evidenced by nuclear γH2AX foci formation. Moreover, overexpression of SATB2 significantly alleviated the senescence of osteoporotic BMSCs in vitro. Importantly, transplantation of SATB2-modified BMSCs significantly attenuated ovariectomy-induced alveolar bone loss in vivo. Together, our results revealed that SATB2 is a critical regulator of alveolar BMSC senescence, and its overexpression decreases these senescent changes both in vitro and in vivo. SATB2-modified BMSC delivery could be a viable and promising therapeutic strategy for alveolar bone loss induced by estrogen-deficient osteoporosis.
Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, China; Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, China.
Rongyao
R
Xu
Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, China; Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, China.
Zongyun
Z
Fu
Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, China; Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, China.
Xue
X
Liu
Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, China; Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, China.
Tao
T
Xiao
Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, China.
Ping
P
Zhang
Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, China.
Yifei
Y
Du
Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, China.
Hua
H
Yuan
Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, China.
Jie
J
Cheng
Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, China; Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, China. Electronic address: jhb@njmu.edu.cn.
Hongbing
H
Jiang
D000375:Aging / Q000473:pathology*; D016301:Alveolar Bone Loss / Q000517:prevention & control*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001842:Bone and Bones / Q000473:pathology; D002454:Cell Differentiation; D004195:Disease Models, Animal; D005260:Female; D036961:Matrix Attachment Region Binding Proteins / Q000235:genetics / Q000378:metabolism*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D010024:Osteoporosis / Q000517:prevention & control / Q000628:therapy; D010052:Ovariectomy / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D015415:Biomarkers; D036961:Matrix Attachment Region Binding Proteins; C586446:SATB2 protein, rat; D014157:Transcription Factors
Alveolar bone loss; Cell therapy; Osteoporosis; Senescence; Special AT-rich binding protein 2 (SATB2)