title: Genes with greater up-regulation in the fracture callus of older rats with delayed healing.
abstract: The rate of bone formation to bridge a fracture gap slows with age. To explore potential pathogenic mechanisms and possible negative-feedback responses by the skeleton to this reduced rate of healing, mRNA transcripts up-regulated more and/or longer were studied in older rats with delayed healing. Female rats at 6 (young), 26 (adult), and 52 (old) weeks of age received unilateral diaphyseal femoral fractures with intramedullary rod stabilization. At 0, 0.4, 1, 2, 4, and 6 weeks after fracture, the fracture site was harvested. Total RNA was extracted, cRNA was prepared, and the cRNA was hybridized to 54 Affymetrix U34A microarrays (three arrays/age/time point). Transcripts for 180 genes were identified as up-regulated more and/or longer in old rats with delayed fracture healing. Of these, 60 were selected for more intense review. Significantly more and/or longer expression was seen in genes related to myofibroblasts, cell proliferation, calcification inhibition, TGF-beta activity, lipid metabolism, cell adhesion, and the cytoskeleton. Further study is needed to determine if these up-regulated transcripts are related to the pathological processes which slow healing or are related to attempts by the fracture tissue to stimulate bone to bridge the fracture gap.
authors.affiliation: Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Carolinas Medical Center, Charlotte, North Carolina 28232-2861, USA.
authors.forename: Martha H
authors.initials: MH
authors.lastname: Meyer
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Meyer
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism / Q000502:physiology; D002146:Bony Callus / Q000378:metabolism*; D002448:Cell Adhesion / Q000235:genetics / Q000502:physiology; D005260:Female; D017102:Fracture Healing / Q000235:genetics* / Q000502:physiology*; D050723:Fractures, Bone / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism / Q000235:genetics / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics / Q000502:physiology*
chemical_list: D000199:Actins; D001057:Apolipoproteins E; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D001189:Aryl Hydrocarbon Hydroxylases; C095029:cytochrome P-450 CYP4B1