title: let-7 enhances osteogenesis and bone formation while repressing adipogenesis of human stromal/mesenchymal stem cells by regulating HMGA2.
abstract: Bone and fat cells share a common progenitor, stromal/mesenchymal stem cells (MSCs), that can differentiate into osteoblasts or adipocytes. Osteogenesis and adipogenesis of MSCs maintain homeostasis under physiological conditions. The disruption of this homeostasis leads to bone-related metabolic diseases. For instance, reduction in bone formation, which is usually accompanied by an increase in bone marrow adipogenesis, occurs with aging, immobility, or osteoporosis. Thus, it is crucial to gain an understanding of how osteogenic and adipogenic lineages of MSCs are regulated. Here, we present evidence that let-7 is a positive regulator of bone development. Using gain- and loss-of-function approaches, we demonstrate that let-7 markedly promotes osteogenesis and suppresses adipogenesis of MSCs in vitro. Moreover, let-7 could promote ectopic bone formation of MSCs in vivo. Subsequent studies further demonstrated that let-7's effects are mediated through the repression of high-mobility group AT-hook 2 (HMGA2) expression. RNAi depletion of HMGA2 could also enhance osteogenesis and repress adipogenesis. Overall, we found a novel role of let-7/HMGA2 axis in regulating the balance of osteogenesis and adipogenesis of MSCs. Thus, let-7 can be used as a novel therapeutic target for disorders that are associated with bone loss and adipocyte accumulation.
authors.affiliation: 1 Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Center of Excellence in Tissue Engineering, School of Basic Medicine Peking Union Medical College , Beijing, China .
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Wei
authors.forename: Hongling
authors.initials: H
authors.lastname: Li
authors.forename: Shihua
authors.initials: S
authors.lastname: Wang
authors.forename: Tangping
authors.initials: T
authors.lastname: Li
authors.forename: Junfen
authors.initials: J
authors.lastname: Fan
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Liang
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Qin
authors.initials: Q
authors.lastname: Han
authors.forename: Li
authors.initials: L
authors.lastname: Zhu
authors.forename: Linyuan
authors.initials: L
authors.lastname: Fan
authors.forename: Robert Chunhua
authors.initials: RC
authors.lastname: Zhao
mesh_terms: D050156:Adipogenesis; D000818:Animals; D001861:Bone Regeneration; D002478:Cells, Cultured; D005269:Femur / Q000196:embryology / Q000378:metabolism; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D025743:HMGA2 Protein / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D035683:MicroRNAs / Q000502:physiology*; D010012:Osteogenesis; D034622:RNA Interference
chemical_list: D025743:HMGA2 Protein; D035683:MicroRNAs; C487931:mirnlet7 microRNA, human