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Effects of Seipin on Mouse Mesenchymal Stem Cell Osteo-Adipogenic Balance.
Effects of Seipin on Mouse Mesenchymal Stem Cell Osteo-Adipogenic Balance.
- Source :
-
Stem cells and development [Stem Cells Dev] 2024 Apr; Vol. 33 (7-8), pp. 177-188. - Publication Year :
- 2024
-
Abstract
- Seipin deficiency is an important cause of type 2 Berardinelli-Seip congenital dyslipidemia (BSCL2). BSCL2 is a severe lipodystrophy syndrome with lack of adipose tissue, hepatic steatosis, insulin resistance, and normal or higher bone mineral density. Bone marrow mesenchymal stem cells (BMSCs) are believed to maintain bone and fat homeostasis by differentiating into osteoblasts and adipocytes. We aimed to explore the role of seipin in the osteogenic/adipogenic differentiation balance of BMSCs. Seipin loxP/loxP mice are used to explore metabolic disorders caused by seipin gene mutations. Compared with wild-type mice, subcutaneous fat deficiency and ectopic fat accumulation were higher in seipin knockout mice. Microcomputed tomography of the tibia revealed the increased bone content in seipin knockout mice. We generated seipin-deficient BMSCs in vitro and revealed that lipogenic genes are downregulated and osteogenic genes are upregulated in seipin-deficient BMSCs. In addition, peroxisome proliferator-activated receptor gamma (PPARĪ³) signaling is reduced in seipin-deficient BMSCs, while using the PPARĪ³ activator increased the lipogenic differentiation and decreased osteogenic differentiation of seipin-deficient BMSCs. Our findings indicated that bone and lipid metabolism can be regulated by seipin through modulating the differentiation of mesenchymal stem cells. Thus, a new insight of seipin mutations in lipid metabolism disorders was revealed, providing a prospective strategy for MSC transplantation-based treatment of BSCL2.
- Subjects :
- Animals
Mice
Cell Differentiation genetics
Mice, Knockout
Osteogenesis genetics
PPAR gamma genetics
PPAR gamma metabolism
X-Ray Microtomography
GTP-Binding Protein gamma Subunits genetics
GTP-Binding Protein gamma Subunits metabolism
Heterotrimeric GTP-Binding Proteins genetics
Heterotrimeric GTP-Binding Proteins metabolism
Mesenchymal Stem Cells metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1557-8534
- Volume :
- 33
- Issue :
- 7-8
- Database :
- MEDLINE
- Journal :
- Stem cells and development
- Publication Type :
- Academic Journal
- Accession number :
- 38386508
- Full Text :
- https://doi.org/10.1089/scd.2023.0107