title: Increased osteogenesis in osteoporotic bone marrow stromal cells by overexpression of leptin.
abstract: Osteoporosis leads to increased bone fractures and net bone loss, in part because of the dysfunction of bone marrow stromal cells (BMSCs). Leptin is an adipokine that plays important roles in many biological processes, including the regulation of the actions of mesenchymal stem cells. Our aim is to investigate the osteogenic effects of leptin in osteoporotic BMSCs in vitro and in vivo. The leptin gene was transferred into BMSCs isolated from osteoporotic rats by using recombinant adenoviruses. Once the gene and protein expression of leptin had been confirmed, MTT assays were performed; leptin overexpression was confirmed not to affect the viability of osteoporotic BMSCs. However, alkaline phosphatase (ALP) activity measurements, Alizarin red staining and analyses by quantitative real-time reverse transcription with the polymerase chain reaction revealed that leptin upregulated ALP activity, mineral deposition and the mRNA levels of runt-related transcription factor 2, ALP and collagen type І. Lastly, the effects of leptin on osteogenic differentiation were assessed in vivo. Cells transfected with leptin exhibited increased osteogenic differentiation and enhanced formation of bone-like structures. This study thus reveals, for the first time, that the overexpression of leptin in osteoporotic BMSCs (1) enhances their capacity to differentiate into osteoblasts and to form bone-like tissue and (2) might be a useful skeletal regenerative therapy in osteoporotic patients.
authors.affiliation: School and Hospital of Stomatology, Fujian Medical University, No. 246, Yangqiaozhong Road, Gulou District, Fuzhou City, Fujian Province, 350002, China.
authors.forename: Baoyu
authors.initials: B
authors.lastname: Zheng
authors.forename: Jun
authors.initials: J
authors.lastname: Jiang
authors.forename: Kai
authors.initials: K
authors.lastname: Luo
authors.forename: Lingling
authors.initials: L
authors.lastname: Liu
authors.forename: Minkui
authors.initials: M
authors.lastname: Lin
authors.forename: Yulin
authors.initials: Y
authors.lastname: Chen
authors.forename: Fuhua
authors.initials: F
authors.lastname: Yan
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D001842:Bone and Bones / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D020738:Leptin / Q000235:genetics / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010006:Osteoblasts / Q000166:cytology*; D010012:Osteogenesis / Q000502:physiology*; D010024:Osteoporosis / Q000378:metabolism; D017207:Rats, Sprague-Dawley
chemical_list: D020738:Leptin