title: Global gene profiling reveals a downregulation of BMP gene expression in experimental atrophic nonunions compared to standard healing fractures.
abstract: Nonunion is a challenging problem that may occur following certain bone fractures. However, there has been little investigation of the molecular basis of nonunions. Bone morphogenetic proteins (BMPs) play a significant role in osteogenesis. However, little is known about the expression patterns of BMPs in abnormal bone healing that results in nonunion formation. These facts prompted us to investigate and compare the gene expression patterns of BMPs and their antagonists in standard healing fractures and nonunions using rat experimental models. Standard closed healing fractures and experimental atrophic nonunions produced by periosteal cauterization at the fracture site were created in rat femurs. At postfracture days 3, 7, 10, 14, 21, and 28, total RNA was extracted from the callus of standard healing fracture and fibrous tissue of nonunion (n=4 per each time point and each group). Gene expression of BMPs, BMP antagonists, and other regulatory molecules were studied by methods including Genechip microarray and real-time quantitative RT-PCR. Gene expression of BMP-2, 3, 3B, 4, 6, 7, GDF-5, 7, and BMP antagonists noggin, drm, screlostin, and BAMBI were significantly lower in nonunions compared to standard healing fractures at several time points. Downregulation in expression of osteogenic BMPs may account for the nonunions of fracture. The balance between BMPs and their endogenous antagonists is critical for optimal fracture healing.
authors.affiliation: Center for Tissue Regeneration and Repair, Department of Orthopaedic Surgery, University of California, Davis, 4860 Y Street, Suite 3800, Sacramento, California 95817, USA.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Niikura
authors.forename: David J
authors.initials: DJ
authors.lastname: Hak
authors.forename: A Hari
authors.initials: AH
authors.lastname: Reddi
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D016207:Cytokines; D015536:Down-Regulation; D005264:Femoral Fractures / Q000378:metabolism*; D017102:Fracture Healing / Q000235:genetics / Q000502:physiology*; D005596:Fractures, Closed / Q000378:metabolism*; D005599:Fractures, Ununited / Q000378:metabolism*; D020869:Gene Expression Profiling; D005819:Genetic Markers; D006023:Glycoproteins / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011506:Proteins; D051381:Rats; D020318:Rats, Long-Evans; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000099176:Noggin Protein
chemical_list: D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D016207:Cytokines; D005819:Genetic Markers; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011506:Proteins; D000099176:Noggin Protein; C485673:Bambi protein, rat; C107276:Grem1 protein, rat; C486031:Sost protein, rat; C054234:chordin