title: Microarray expression analysis of genes and pathways involved in growth plate cartilage injury responses and bony repair.
abstract: The injured growth plate cartilage is often repaired by a bone bridge which causes bone growth deformities. Whilst previous studies have identified sequential inflammatory, fibrogenic, osteogenic and bone remodelling responses involved in the repair process, the molecular pathways which regulated these cellular events remain unknown. In a rat growth plate injury model, tissue from the injury site was collected across the time-course of bone bridge formation using laser capture microdissection and was subjected to Affymetrix microarray gene expression analysis. Real Time PCR and immunohistochemical analyses were used to confirm changes in levels of expression of some genes identified in microarray. Four major functional groupings of differentially expressed genes with known roles in skeletal development were identified across the time-course of bone bridge formation, including Wnt signalling (SFRP1, SFRP4, β-catenin, Csnk2a1, Tcf7, Lef1, Fzd1, Fzd2, Wisp1 and Cpz), BMP signalling (BMP-2, BMP-6, BMP-7, Chrd, Chrdl2 and Id1), osteoblast differentiation (BMP-2, BMP-6, Chrd, Hgn, Spp1, Axin2, β-catenin, Bglap2) and skeletal development (Chrd, Mmp9, BMP-1, BMP-6, Spp1, Fgfr1 and Traf6). These studies provide insight into the molecular pathways which act cooperatively to regulate bone formation following growth plate cartilage injury and highlight potential therapeutic targets to limit bone bridge formation.
authors.affiliation: Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia.
authors.forename: Carmen E
authors.initials: CE
authors.lastname: Macsai
authors.forename: Kristen R
authors.initials: KR
authors.lastname: Georgiou
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Foster
authors.forename: Andrew C W
authors.initials: AC
authors.lastname: Zannettino
authors.forename: Cory J
authors.initials: CJ
authors.lastname: Xian
mesh_terms: D000818:Animals; D002356:Cartilage / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006132:Growth Plate / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D061346:Laser Capture Microdissection; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D046228:Microarray Analysis / Q000379:methods*; D010012:Osteogenesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D000072042:Salter-Harris Fractures; D015398:Signal Transduction / Q000235:genetics*; D013997:Time Factors; D015854:Up-Regulation / Q000235:genetics; D014945:Wound Healing / Q000235:genetics*; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C500646:Sfrp1 protein, rat; D000094742:Secreted Frizzled-Related Proteins