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Dominant negative Bmp5 mutation reveals key role of BMPs in skeletal response to mechanical stimulation

Ho, AM and Marker, PC and Peng, H and Quintero, AJ and Kingsley, DM and Huard, J (2008) Dominant negative Bmp5 mutation reveals key role of BMPs in skeletal response to mechanical stimulation. BMC Developmental Biology, 8.

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Abstract

Background. Over a hundred years ago, Wolff originally observed that bone growth and remodeling are exquisitely sensitive to mechanical forces acting on the skeleton. Clinical studies have noted that the size and the strength of bone increase with weight bearing and muscular activity and decrease with bed rest and disuse. Although the processes of mechanotransduction and functional response of bone to mechanical strain have been extensively studied, the molecular signaling mechanisms that mediate the response of bone cells to mechanical stimulation remain unclear. Results. Here, we identify a novel germline mutation at the mouse Bone morphogenetic protein 5 (Bmp5) locus. Genetic analysis shows that the mutation occurs at a site encoding the proteolytic processing sequence of the BMP5 protein and blocks proper processing of BMP5. Anatomic studies reveal that this mutation affects the formation of multiple skeletal features including several muscle-induced skeletal sites in vivo. Biomechanical studies of osteoblasts from these anatomic sites show that the mutation inhibits the proper response of bone cells to mechanical stimulation. Conclusion. The results from these genetic, biochemical, and biomechanical studies suggest that BMPs are required not only for skeletal patterning during embryonic development, but also for bone response and remodeling to mechanical stimulation at specific anatomic sites in the skeleton. © 2008 Ho et al; licensee BioMed Central Ltd.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Ho, AM
Marker, PC
Peng, H
Quintero, AJ
Kingsley, DM
Huard, J
Centers: Other Centers, Institutes, Offices, or Units > Stem Cell Research Center
Date: 30 April 2008
Date Type: Publication
Journal or Publication Title: BMC Developmental Biology
Volume: 8
DOI or Unique Handle: 10.1186/1471-213x-8-35
Schools and Programs: School of Medicine > Biochemistry and Molecular Genetics
Swanson School of Engineering > Bioengineering
Refereed: Yes
MeSH Headings: Animals; Body Patterning; Bone Morphogenetic Protein 5; Bone Morphogenetic Proteins--genetics; Bone Remodeling--genetics; Cells, Cultured; Embryo, Mammalian; Female; Fibroblasts--metabolism; Fluorescent Antibody Technique, Indirect; Gene Expression; Genes, Dominant; Germ-Line Mutation; In Situ Hybridization; Male; Mice; Mice, Inbred C57BL; Osteoblasts--metabolism; Osteogenesis--genetics; Stress, Mechanical
Other ID: NLM PMC2335095
PubMed Central ID: PMC2335095
PubMed ID: 18380899
Date Deposited: 15 May 2014 20:36
Last Modified: 20 Dec 2018 00:55
URI: http://d-scholarship.pitt.edu/id/eprint/21590

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