TY - JOUR
T1 - Potential roles of growth factor PDGF-BB in the bony repair of injured growth plate
AU - Chung, Rosa
AU - Foster, Bruce K.
AU - Zannettino, A. C W
AU - Xian, Cory J.
N1 - Funding Information:
The project was funded in part by grants from Bone Growth foundation (BGF), Channel-7 Children's Research Foundation of South Australia (to CJX and BKF), and from the Australian National Health and Medical Research Council (NHMRC) (to CJX and BKF). The authors would like to thank Ms Chia-ming Fan and Ms Jo Cool for their assistance with the animal trial.
PY - 2009/5
Y1 - 2009/5
N2 - 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. Crown
AB - 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. Crown
KW - Bone marrow stromal cells
KW - Growth plate
KW - Imatinib
KW - Injury and repair
KW - PDGF-BB
UR - http://www.scopus.com/inward/record.url?scp=63449134564&partnerID=8YFLogxK
U2 - 10.1016/j.bone.2009.01.377
DO - 10.1016/j.bone.2009.01.377
M3 - Article
C2 - 19442606
AN - SCOPUS:63449134564
SN - 8756-3282
VL - 44
SP - 878
EP - 885
JO - Bone
JF - Bone
IS - 5
ER -