Редактирование: SATB2

DNA-binding protein SATB2 (Special AT-rich sequence-binding protein 2) [KIAA1034]

==Publications==

{{medline-entry
|title=microRNA-31 inhibition partially ameliorates the deficiency of bone marrow stromal cells from cleidocranial dysplasia.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30506733
|abstract=Cleidocranial dysplasia (CCD) in humans is an autosomal-dominant skeletal dysplasia caused by heterozygous mutations of the runt-related transcription factor 2 ([[RUNX2]]) and significantly increases the risk of osteoporosis. Increasing evidence demonstrates that the dysfunction of bone marrow stromal cells from CCD patients (BMSCs-CCD) contributes to the bone deficiency, but the characteristics of BMSCs-CCD and the mechanisms that underlie their properties remain undefined. The clinical manifestations of three CCD patients were collected and the mutations of [[RUNX2]] were analyzed. The properties of proliferation, osteogenesis, stemness, and senescence of BMSCs-CCD were compared with that of BMSCs from healthy donors. The expression of microRNA-31 ( miR-31) between BMSCs-CCD and BMSCs was measured and lentivirus-carried miR-31 inhibitor was used to determine the role of miR-31 in BMSCs-CCD both in vitro and in vivo. The molecular mechanisms underlying [[RUNX2]]-miR31 and miR-31 targeting stemness and senescence of BMSCs-CCD were also explored. We identified two mutation sites of [[RUNX2]] via exome sequencing from 2 of 3 Chinese CCD patients with typical clinical presentations. Compared with BMSCs from healthy donors, BMSCs-CCD displayed significantly attenuated proliferation, osteogenesis and stemness, and enhanced senescence. Meanwhile, miR-31 knockdown could ameliorate these deficiency phenotypes of BMSCs-CCD by regulating [[SATB2]], [[BMI1]], CDKN, and [[SP7]]. Mechanistically, [[RUNX2]] directly repressed miR-31 expression, and therefore [[RUNX2]] haploinsufficiency in CCD leading to miR-31 upregulation contributed to the deficiency of BMSCs-CCD. miR-31 inhibition in BMSCs-CCD showed enhanced osteogenesis through heterotopic subcutaneous implantation in the nude mice. Our results show the functional deficiencies of BMSCs-CCD and a potential role of miR-31 in BMSCs-CCD deficiencies. The application of miR-31 inhibitor in BMSCs-CCD might lend hope for developing BMSC-based therapeutic approaches against CCD-associated skeletal diseases.
|mesh-terms=* Adolescent
* Animals
* Base Sequence
* Cell Proliferation
* Child
* Choristoma
* Cleidocranial Dysplasia
* Core Binding Factor Alpha 1 Subunit
* Haploinsufficiency
* Humans
* Mesenchymal Stem Cells
* Mice, Inbred BALB C
* Mice, Nude
* MicroRNAs
* Mutation
* Organ Size
* Osteogenesis
* Up-Regulation
* Young Adult
|keywords=* bone marrow stromal cells
* cleidocranial dysplasia
* microRNA-31
* osteogenesis
* senescence
* stemness
|full-text-url=https://sci-hub.do/10.1002/jcb.28223
}}
{{medline-entry
|title=[[SATB2]]-Nanog axis links age-related intrinsic changes of mesenchymal stem cells from craniofacial bone.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27632702
|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.
|mesh-terms=* Age Factors
* Aging
* Animals
* Bone and Bones
* Gene Expression
* Humans
* Matrix Attachment Region Binding Proteins
* Mesenchymal Stem Cells
* Nanog Homeobox Protein
* Osteogenesis
* Rats
* Transcription Factors
|keywords=* aging
* bone loss
* bone mesenchymal stem cells
* cytotherapy
* pluripotency
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5076449
}}
{{medline-entry
|title=Transplantation of osteoporotic bone marrow stromal cells rejuvenated by the overexpression of [[SATB2]] prevents alveolar bone loss in ovariectomized rats.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27599698
|abstract=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.
|mesh-terms=* Aging
* Alveolar Bone Loss
* Animals
* Biomarkers
* Bone and Bones
* Cell Differentiation
* Disease Models, Animal
* Female
* Matrix Attachment Region Binding Proteins
* Mesenchymal Stem Cell Transplantation
* Mesenchymal Stem Cells
* Osteoporosis
* Ovariectomy
* Rats
* Rats, Sprague-Dawley
* Transcription Factors
|keywords=* Alveolar bone loss
* Cell therapy
* Osteoporosis
* Senescence
* Special AT-rich binding protein 2 (SATB2)
|full-text-url=https://sci-hub.do/10.1016/j.exger.2016.09.001
}}
{{medline-entry
|title=Roles of [[SATB2]] in site-specific stemness, autophagy and senescence of bone marrow mesenchymal stem cells.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25200657
|abstract=Craniofacial bone marrow mesenchymal stem cells (BMSCs) display some site-specific properties that differ from those of BMSCs derived from the trunk and appendicular skeleton, but the characteristics of craniofacial BMSCs and the mechanisms that underlie their properties are not completely understood. Previous studies indicated that special AT-rich binding protein 2 ([[SATB2]]) may be a potential regulator of craniofacial skeletal patterning and site-specific osteogenic capacity. Here, we investigated the stemness, autophagy, and anti-aging capacity of mandible-derived BMSCs (M-BMSCs) and tibia-derived BMSCs (T-BMSCs) and explored the role of [[SATB2]] in regulating these properties. M-BMSCs not only possessed stronger expression of [[SATB2]] and stemness markers (pluripotency genes, such as Nanog, OCT-4, Sox2, and Nestin) but also exhibited stronger autophagy and anti-aging capacities under normal or hypoxia/serum deprivation conditions compared to T-BMSCs. Exogenous expression of [[SATB2]] in T-BMSCs significantly enhanced the expression of pluripotency genes as well as autophagy and anti-aging capacity. Moreover, [[SATB2]] markedly enhanced osteogenic differentiation of BMSCs in vitro, and promoted bone defect regeneration and the survival of BMSCs that were transplanted into mandibles with critical size defects. Mechanistically, [[SATB2]] upregulates pluripotency genes and autophagy-related genes, which in turn activate the mechanistic target of rapamycin signaling pathway. Collectively, our results provide novel evidence that site-specific BMSCs have distinct biological properties and suggest that [[SATB2]] plays a potential role in regulating the stemness, autophagy, and anti-aging properties of craniofacial BMSCs. The application of [[SATB2]] to manipulate stem cells for the reconstruction of bone defects might represent a new approach.
|mesh-terms=* Aging
* Animals
* Autophagy
* Bone Marrow Cells
* Cellular Senescence
* Humans
* Mandible
* Matrix Attachment Region Binding Proteins
* Mesenchymal Stem Cells
* Mice
* Tibia
* Transcription Factors

|full-text-url=https://sci-hub.do/10.1002/jcp.24792
}}