Expression of proinflammatory cytokines and growth factors at the injured growth plate cartilage in young rats

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-1beta expression peaked at 8-16 h, and TNF-alpha and TGF-beta1 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-alpha, FGF-2, and TGF-beta1 rose again during days 25-35, and IGF-1 and bone matrix protein osteocalcin elevated from days 7 to 35. The positive changes in expression of IL-1beta, TNF-alpha, TGF-beta1, and IGF-1 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. Crown Copyright (C) 2004 Published by Elsevier Inc. All rights reserved.