title: Transgenic overexpression of bone morphogenetic protein 11 propeptide in skeleton enhances bone formation.
abstract: Bone morphogenetic protein 11 (BMP11) is a key regulatory protein in skeletal development. BMP11 propeptide has been shown to antagonize GDF11 activity in vitro. To explore the role of BMP11 propeptide in skeletal formation in vivo, we generated transgenic mice with skeleton-specific overexpression of BMP11 propeptide cDNA. The mice showed a transformation of the seventh cervical vertebra into a thoracic vertebra in our previous report. Presently, further characterizations of the transgenic mice indicated that ossification in calvatia was dramatically enhanced in transgenic fetuses at 16.5 dpc in comparison with their wild-type littermates. At 10 weeks of age, bone mineral content and bone mineral density were significantly (P<0.05) higher in transgenic mice than that in their wild-type littermates based on dual energy X-ray absorptiometry analysis. The relative trabecular bone volume measured by histological analysis was dramatically increased in transgenic mice compared with their wild-type littermates. The enhanced bone formations in the transgenic mice appear to result from increase osteoblast activities as the expressions of four osteoblast markers - α1 type 1 collagen, osteocalcin, alkaline phosphatase and phex were significantly higher in transgenic fetuses than that in their wild-type littermates. These results suggest that over-expression of BMP11 propeptide stimulates bone formation by increasing osteoblast cell functions.
authors.affiliation: Department of Human Nutrition, Food and Animal Sciences, University of Hawaii at Manoa, Honolulu, HI, USA. lizicongcong@163.com
authors.forename: Zicong
authors.initials: Z
authors.lastname: Li
authors.forename: Fang
authors.initials: F
authors.lastname: Zeng
authors.forename: Alva D
authors.initials: AD
authors.lastname: Mitchell
authors.forename: Yong Soo
authors.initials: YS
authors.lastname: Kim
authors.forename: Zhenfang
authors.initials: Z
authors.lastname: Wu
authors.forename: Jinzeng
authors.initials: J
authors.lastname: Yang
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015519:Bone Density; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D015870:Gene Expression; D055412:Growth Differentiation Factors / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics*; D019076:Transgenes
chemical_list: D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; C119153:Gdf11 protein, mouse; D055412:Growth Differentiation Factors
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