期刊
JOURNAL OF BONE AND MINERAL RESEARCH
卷 32, 期 3, 页码 508-521出版社
WILEY
DOI: 10.1002/jbmr.3009
关键词
SLC7A11; SULFASALAZINE; OSTEOGENIC DIFFERENTIATION; BONE MORPHOGENETIC PROTEIN; OSTEOPOROSIS
资金
- National Natural Science Foundation of China [81570953, 81500822]
- Program for New Century Excellent Talents in University from Ministry of Education [NCET-11-0026]
- PKU School of Stomatology for Talented Young Investigators [PKUSS20140109]
- Construction Program for National Key Clinical Specialty from National Health and Family Planning Commission of China
An imbalance in osteogenesis and adipogenesis is a crucial pathological factor in the development of osteoporosis. Many attempts have been made to develop drugs to prevent and treat this disease. In the present study, we investigated the phenomenon whereby downregulation of SLC7A11 significantly enhanced the osteogenic differentiation of mesenchymal stem cells (MSCs) in vitro, and promoted the bone formation in vivo. Sulfasalazine (SAS), an inhibitor of SLC7A11, increased the osteogenic potential effectively. Mechanistically, inhibition of SLC7A11 by SAS treatment or knockdown of SLC7A11 increased BMP2/ 4 expression dramatically. In addition, we detected increased Slc7a11 expression in bone marrow MSCs of ovariectomized (OVX) mice. Remarkably, SAS treatment attenuated bone loss in ovariectomized mice. Together, our data suggested that SAS could be used to treat osteoporosis by enhancing osteogenic differentiation of MSCs. (C) 2016 American Society for Bone and Mineral Research.
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