Connective tissue growth factor and insulin-like growth factor 2 show upregulation in early growth plate radiorecovery response following irradiation.
BACKGROUND
The growth plate response following radiotherapy is poorly understood. In particular, little is known about the changes in growth plate growth factors and cytokines following irradiation. The hypothesis was that a limited number of growth factors and cytokines play a role in growth plate proliferative and hypertrophic chondrocyte radio-recovery.


METHODS
The right limbs of 6 rats were irradiated (17.5 Gy), leaving the left limbs as controls. Limbs were harvested 1 (n = 3) and 2 (n = 3) weeks later. Microarrays were constructed from chondrocytes obtained by laser microdissection from the proliferative zone (PZ) and the hypertrophic zone (HZ) of normal and irradiated tibia growth plates. Real-time PCR was used to confirm the expression of parathyroid hormone receptor 1 (Pthr1), connective tissue growth factor (CTGF), insulin-like growth factor I receptor (IGF1R), insulin-like growth factor II (IGF2), interleukin 17beta (IL17b) and chemokine ligand 12 (CXCL12).


CONCLUSIONS
IGF2 is upregulated in the PZ and CTGF is upregulated in both the PZ and HZ 1 week after irradiation, prior to the histomorphometric appearance of growth plate recovery in this immature animal radiation model, supporting their role in stimulating early return of the growth plate. By 2 weeks after irradiation, a number of growth factors and cytokines, including CTGF and Pthr1 in both zones, CXCL12 and its receptor in the PZ, and IL17b and bone morphogenetic protein 2 in the HZ, show upregulation, suggesting a possible later role in radiorecovery. The effects of irradiation on Pthr1, CTGF, IGF2 and CXCL12 in PZ and Pthr1, CTGF, IL17b and IGF1R in the HZ determined by microarray and real-time RT-PCR was highly correlated (r = 0.797, p < 0.05 in the PZ and r = 0.875, p < 0.01 in the HZ, respectively).
Wang
Yan
Y
Musculoskeletal Sciences Research Laboratory, Department of Orthopedic Surgery, Syracuse, NY 13202, USA.
Zhang
Mingliang
M
Middleton
Frank A
FA
Horton
Jason A
JA
Pritchard
Meredith
M
Spadaro
Joseph A
JA
Farnum
Cornelia E
CE
Damron
Timothy A
TA
D000818:Animals; D015415:Biomarkers; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics; D019902:Chondrocytes / Q000166:cytology / Q000528:radiation effects*; D020219:Chondrogenesis / Q000235:genetics / Q000528:radiation effects; D055513:Connective Tissue Growth Factor; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics*; D006132:Growth Plate / Q000166:cytology / Q000254:growth & development / Q000528:radiation effects*; D017874:Immediate-Early Proteins / Q000235:genetics*; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D009693:Nucleic Acid Hybridization / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D011833:Radiation Injuries, Experimental / Q000235:genetics / Q000534:rehabilitation*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000235:genetics; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013977:Tibia / Q000166:cytology / Q000254:growth & development / Q000528:radiation effects; D015854:Up-Regulation
D015415:Biomarkers; C526316:CCN2 protein, rat; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D044168:Receptor, Parathyroid Hormone, Type 1; D055513:Connective Tissue Growth Factor; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1