Mesenchymal stem cells （MSCs） are considered as the developmental origin of multiple Uneage cells including osteocytes, adipocytes, and muscle cells. Previous studies demonstrated that the PH domain.containing prote...Mesenchymal stem cells （MSCs） are considered as the developmental origin of multiple Uneage cells including osteocytes, adipocytes, and muscle cells. Previous studies demonstrated that the PH domain.containing protein CKIP-1 plays an important role in the devel- opment of osteobiasts and cardiomyocytes. However, whether CKIP-1 is involved in the generation of adipocytes as weU as the MSC differentiation remains unknown. Here we show that CKIP-1 is a novel regulator of MSCs differentiating into adipocytes. MSCs derived from CKIP-l-deficient mice display enhanced adipogenesis upon induction. Further analysis showed that CKIP-1 interacts with the histone deacetylase HDAC1 in the nucleus and inhibits the transcription of CCAAT/enhancer-binding protein α （C/EBPcx）, which is a crucial adipogenic transcription factor. Ectopic expression of CKI P-1 in a MSC-Uke cell line C3H/10T1/2 reduced the gener- ation of adipocytes due to suppression of adipogenic factors, including C/EBPα. Moreover, CKI P-l-deficient mice showed an increase in body weight and white adipose tissue gains when fed on a high-fat diet. Collectively, these results suggest that CKIP-1 is a novel inhibitor of MSC-originated adipogenesis by enhancing HDACl-associated repression of C/EBPα.展开更多
文摘Mesenchymal stem cells （MSCs） are considered as the developmental origin of multiple Uneage cells including osteocytes, adipocytes, and muscle cells. Previous studies demonstrated that the PH domain.containing protein CKIP-1 plays an important role in the devel- opment of osteobiasts and cardiomyocytes. However, whether CKIP-1 is involved in the generation of adipocytes as weU as the MSC differentiation remains unknown. Here we show that CKIP-1 is a novel regulator of MSCs differentiating into adipocytes. MSCs derived from CKIP-l-deficient mice display enhanced adipogenesis upon induction. Further analysis showed that CKIP-1 interacts with the histone deacetylase HDAC1 in the nucleus and inhibits the transcription of CCAAT/enhancer-binding protein α （C/EBPcx）, which is a crucial adipogenic transcription factor. Ectopic expression of CKI P-1 in a MSC-Uke cell line C3H/10T1/2 reduced the gener- ation of adipocytes due to suppression of adipogenic factors, including C/EBPα. Moreover, CKI P-l-deficient mice showed an increase in body weight and white adipose tissue gains when fed on a high-fat diet. Collectively, these results suggest that CKIP-1 is a novel inhibitor of MSC-originated adipogenesis by enhancing HDACl-associated repression of C/EBPα.
