Potential roles of growth factor PDGF-BB in the bony repair of injured growth plate.
Injured growth plate cartilage is often repaired by bony tissue resulting in impaired bone growth in children. Using a rat injury model, our previous studies show that following the injury-induced initial inflammatory response, an influx of mesenchymal-like cells occurs within the growth plate injury site prior to formation of bony tissue. As platelet-derived growth factor (PDGF-BB) is a potent chemotactic factor of mesenchymal cells during skeletal tissue repair, we examined its role during the early fibrogenic response and the subsequent bony repair of injured growth plate. Following growth plate injury, rats received daily injection of the PDGF receptor (PDGFR) inhibitor, Imatinib, for 7 days. Immunohistochemical analysis of injured growth plate at day 1 showed the presence of PDGF-BB expression in some inflammatory cells, while at day 4 PDGFR was expressed by a proportion of the infiltrating mesenchymal cells at the injury site. By day 4, PDGFR inhibition reduced mesenchymal infiltrate (P<0.05); by day 14, Imatinib-treated rats exhibited less bony trabeculae and cartilaginous repair tissues, fewer osteoclasts and less bone marrow (BM) at the injury site, compared to vehicle controls (P<0.01). In vitro "scratch" migration assays with rat BM mesenchymal cells revealed that recombinant PDGF-BB increased cell migration into the "wound" (P<0.05), while Imatinib inhibited this chemotactic response. Quantitative RT-PCR analysis showed that Imatinib treatment decreased expression of the cartilage and bone related genes, Col2a1 and osteocalcin, respectively. These results suggest that PDGF-BB contributes to growth plate injury repair by promoting mesenchymal progenitor cell infiltration, the chondrogenic and osteogenic responses, and remodelling of the repair tissues.
Chung
Rosa
R
Department of Orthopaedic Surgery, Women's and Children's Hospital, North Adelaide, Australia. rosa.chung@adelaide.edu.au
Foster
Bruce K
BK
Zannettino
Andrew C W
AC
Xian
Cory J
CJ
D000818:Animals; D000077214:Becaplermin; D001549:Benzamides; D001854:Bone Marrow Cells / Q000166:cytology; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D024043:Collagen Type II / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006132:Growth Plate / Q000187:drug effects / Q000378:metabolism*; D000068877:Imatinib Mesylate; D007150:Immunohistochemistry; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology; D015675:Osteocalcin / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000072042:Salter-Harris Fractures; D017154:Stromal Cells / Q000166:cytology
D001549:Benzamides; D024043:Collagen Type II; D010879:Piperazines; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011743:Pyrimidines; D015675:Osteocalcin; D000077214:Becaplermin; D000068877:Imatinib Mesylate; D020797:Receptor, Platelet-Derived Growth Factor beta