Roles of COX-2 and iNOS in the bony repair of the injured growth plate cartilage.
Growth plate injuries often lead to bone growth defects, which primarily occur due to bony repair at injury sites. Bony repair is preceded by an injury-induced inflammatory response, which could play a role in regulating the repair process. Here, roles of two inflammatory mediators, cyclo-oxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS), in the injury responses were analysed by examining their gene expression and effects of blocking their activities, respectively, with celecoxib and aminoguanidine during 2 days prior to and until 7 days after injury in a rat tibial growth plate injury model. Quantitative RT-PCR assays revealed upregulated expression of COX-2 on days 1 and 4 and iNOS on day 1. Histological analysis of injury sites revealed significant reductions in inflammatory infiltrate (particularly neutrophils) on day 1 in treated groups compared to saline control. While bony tissue proportions at injury sites were unaffected by either treatment, mesenchymal tissue proportions were larger but cartilaginous tissue proportions were smaller on day 8 (though statistically insignificant), and bone remodelling appeared delayed with a smaller bone marrow proportion on day 14 in both treatment groups. These findings suggest that COX-2 and iNOS mediate injury-induced inflammatory response, and may play a role in enhancing mesenchymal cell differentiation to cartilaginous cells and in promoting bone remodelling during bony repair of growth plate injury sites. Furthermore, increased expression of cartilage-related (collagen-2, collagen-10, SOX-9) and bone-related molecules (osteocalcin, cbfalpha-1) suggest involvement of both endochondral and direct bone formation mechanisms during bony repair.
Arasapam
G
G
Department of Physiology, University of Adelaide, Adelaide, South Australia, Australia.
Scherer
M
M
Cool
J C
JC
Foster
B K
BK
Xian
C J
CJ
D000818:Animals; D001483:Base Sequence; D016723:Bone Remodeling / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D000068579:Celecoxib; D024043:Collagen Type II / Q000378:metabolism; D024121:Collagen Type X / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D017931:DNA Primers / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017102:Fracture Healing / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects; D006132:Growth Plate / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D006146:Guanidines / Q000494:pharmacology; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism; D007375:Interleukin-1 / Q000235:genetics; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015675:Osteocalcin / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000072042:Salter-Harris Fractures; D013449:Sulfonamides / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D024043:Collagen Type II; D024121:Collagen Type X; D016861:Cyclooxygenase Inhibitors; D017931:DNA Primers; D004791:Enzyme Inhibitors; D006146:Guanidines; D018836:Inflammation Mediators; D007375:Interleukin-1; D011720:Pyrazoles; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; D015675:Osteocalcin; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D000068579:Celecoxib; C004479:pimagedine