Decreased platelet derived growth factor expression during fracture healing in diabetic animals.
Animal model experiments have suggested that diabetes inhibits cell proliferation during fracture healing. Immunohistochemical analysis of proliferating cell nuclear antigen revealed significant reductions in cellular proliferation rates in the fracture callus of spontaneously diabetic BB Wistar rats as compared with healthy BB Wistar rats. Because platelet derived growth factor is associated with the early stage of fracture healing, it was hypothesized that diabetes causes decreased platelet derived growth factor expression during the early phase of fracture healing with a concomitant decrease in cell proliferation. Midshaft femur fractures were created in healthy and spontaneously diabetic BB Wistar rats and analyzed at Days 2, 4, and 7 after fracture for expression of platelet derived growth factor. Immunohistochemistry showed decreased localization of platelet derived growth factor in early diabetic fracture callus compared with healthy controls. Platelet derived growth factor messenger ribonucleic acid levels, as determined by reverse transcription and polymerase chain reaction, also were decreased in early diabetic fractures compared with healthy controls. Therefore the decreased cell proliferation rates associated with diabetic fracture healing are consistent with decreased platelet derived growth factor levels and suggest a causal relationship. These results suggest that diabetes is affecting the early phase of fracture healing by inhibiting cell proliferation through decreasing expression of platelet derived growth factor.
Tyndall
William A
WA
Department of Orthopaedics, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark 07103, USA.
Beam
Heather A
HA
Zarro
Christopher
C
O'Connor
J Patrick
JP
Lin
Sheldon S
SS
D000818:Animals; D002146:Bony Callus / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D004195:Disease Models, Animal; D005264:Femoral Fractures / Q000378:metabolism; D017102:Fracture Healing / Q000502:physiology*; D007150:Immunohistochemistry; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011913:Rats, Inbred BB; D020133:Reverse Transcriptase Polymerase Chain Reaction
D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger