TY - JOUR
T1 - Expression of proinflammatory cytokines and growth factors at the injured growth plate cartilage in young rats
AU - Zhou, Fiona H.
AU - Foster, Bruce K.
AU - Sander, Guy
AU - Xian, Cory J.
N1 - Funding Information:
The authors wish to thank Dr. Wei-Hong Liu (University of Adelaide), Mr. Jonathan Hutton, and Dr. Barry Powell (Children's Health Research Institute, South Australia) for their valuable technical advice and support in real time RT-PCR, and Dr. Sharon Byers (Women's and Children's Hospital) for technical advice on growth plate cartilage dissection. The project was funded by Bone Growth Foundation (BGF) and in part by grants from Channel-7 Children's Research Foundation of South Australia (to CJX and BKF) and from Australian National Health and Medical Research Council (NHMRC) (to CJX). FHZ is a recipient of BGF/Big W PhD scholarship. CJX is a RD Wright Fellow of the NHMRC.
PY - 2004/12
Y1 - 2004/12
N2 - Growth plate, a cartilage-like tissue responsible for bone lengthening in children, has limited abilities to regenerate. After injury, a bony repair often occurs at the injury site, which may lead to growth arrest or angulation of the involved long bone. Our previous study has demonstrated inflammatory, fibrogenic, and osteogenic responses at the injured growth plate; however, the underlying mechanisms remain unclear. In this study, mRNA expression patterns of pro-inflammatory cytokines, growth factors, transcription factors, and matrix proteins were examined by quantitative RT-PCR over a 35-day time period after a drill-hole injury at the proximal tibial growth plate of young rats. During the initial inflammatory phase, IL-1β expression peaked at 8-16 h, and TNF-α and TGF-β1 levels peaked on day 1. During the subsequent fibrogenic response, expression of growth factors FGF-2 and PDGF-B was up-regulated on day 3 whereas levels of collagen-2a and transcription factor Sox9 remained unchanged. In the osteogenic and bone remodeling stages, levels of TNF-α, FGF-2, and TGF-β1 rose again during days 25-35, and IGF-I and bone matrix protein osteocalcin elevated from days 7 to 35. The positive changes in expression of IL-1β, TNF-α, TGF-β1, and IGF-I suggest their possible roles in the early acute inflammatory event and later in the formation and remodeling of the bone bridge. The up-regulation of FGF-2 and PDGF-B, coinciding with mesenchymal cell infiltration, suggests their possible involvement in the intermediate fibrogenic response. The lack of up-regulation of Col-2a and Sox9 refutes the involvement of endochondral ossification but confirms a direct bone formation response during bone bridge formation at the injured growth plate.
AB - Growth plate, a cartilage-like tissue responsible for bone lengthening in children, has limited abilities to regenerate. After injury, a bony repair often occurs at the injury site, which may lead to growth arrest or angulation of the involved long bone. Our previous study has demonstrated inflammatory, fibrogenic, and osteogenic responses at the injured growth plate; however, the underlying mechanisms remain unclear. In this study, mRNA expression patterns of pro-inflammatory cytokines, growth factors, transcription factors, and matrix proteins were examined by quantitative RT-PCR over a 35-day time period after a drill-hole injury at the proximal tibial growth plate of young rats. During the initial inflammatory phase, IL-1β expression peaked at 8-16 h, and TNF-α and TGF-β1 levels peaked on day 1. During the subsequent fibrogenic response, expression of growth factors FGF-2 and PDGF-B was up-regulated on day 3 whereas levels of collagen-2a and transcription factor Sox9 remained unchanged. In the osteogenic and bone remodeling stages, levels of TNF-α, FGF-2, and TGF-β1 rose again during days 25-35, and IGF-I and bone matrix protein osteocalcin elevated from days 7 to 35. The positive changes in expression of IL-1β, TNF-α, TGF-β1, and IGF-I suggest their possible roles in the early acute inflammatory event and later in the formation and remodeling of the bone bridge. The up-regulation of FGF-2 and PDGF-B, coinciding with mesenchymal cell infiltration, suggests their possible involvement in the intermediate fibrogenic response. The lack of up-regulation of Col-2a and Sox9 refutes the involvement of endochondral ossification but confirms a direct bone formation response during bone bridge formation at the injured growth plate.
KW - Bone bridge
KW - Growth factors
KW - Growth plate
KW - Injury
KW - Proinflammatory cytokines
UR - https://www.scopus.com/pages/publications/13844307612
U2 - 10.1016/j.bone.2004.09.014
DO - 10.1016/j.bone.2004.09.014
M3 - Article
C2 - 15589211
AN - SCOPUS:13844307612
SN - 8756-3282
VL - 35
SP - 1307
EP - 1315
JO - Bone
JF - Bone
IS - 6
ER -