Perioperative glucocorticosteroid treatment delays early healing of a mandible wound by inhibiting osteogenic differentiation.
OBJECTIVE
The purpose of this study is to investigate the effects of dexamethasone on repair of a critical size defect of the mandible in male Sprague-Dawley rats.


METHODS
Fifty rats were divided into 2 groups: saline control and dexamethasone-treated groups. A 1 mm × 3 mm full-thickness bone defect was created at the inferior border of the mandible. Saline or dexamethasone was administered once a day for 5 days after postoperative palinesthesia. On days 1, 3, 6, 10 and 17, after cessation of drug administration, 5 samples from each group were analysed. The bone defect healing process was examined and analysed by stereology, radiology, histology and histochemical staining for total collagen, tartrate-resistant acid phosphatase staining for osteoclasts and immunohistochemical staining for the COX-2, RUNX2 and osteocalcin antigens.


RESULTS
The dexamethasone-treated rats exhibited significantly lower radiopacity properties compared to the control rats. Histological staining revealed that the osteogenic differentiation and maturation of a callus in the defect region was significantly delayed from day 1 to day 10 in the dexamethasone group after cessation of drug administration compared to the control group. Consistent with the histological data, the level of total collagen protein was significantly lower in the dexamethasone group than in the control group. However, there was no significant difference between the 2 groups at day 17. Immunohistochemical analysis of COX-2, RUNX2 and osteocalcin expression showed that, at day 1, COX-2 and RUNX2 expression in the dexamethasone group was significantly lower than in the control group. There was no significant difference in osteocalcin expression between the two groups at each time point. There was no significant difference in the number of osteoclasts between the two groups.


CONCLUSIONS
In a model of bone healing of a mandible defect, dexamethasone-treated rats exhibited impaired osteogenic differentiation and maturation due to the inhibition of COX-2, osteogenic gene, RUNX2 and collagen protein expression, which resulted in delayed bone repair. Although perioperative short-term therapy did not exhibit long-term effects on wound healing of the maxillofacial bone, the application of glucocorticoids should be cautiously considered in the clinic.
Department of Oral and Maxillofacial Surgery, School of Stomatology, Nanjing Medical University, Nanjing, Jiangsu 210029, PR China.
Jun
J
Li
Xianwei
X
Wang
Chen
C
Zhou
Laikui
L
Liu
Yunong
Y
Wu
Dongmiao
D
Wang
Hongbing
H
Jiang
D000135:Acid Phosphatase / Q000494:pharmacology*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D003094:Collagen / Q000494:pharmacology; D003907:Dexamethasone / Q000009:adverse effects*; D004195:Disease Models, Animal; D005938:Glucocorticoids / Q000009:adverse effects*; D007527:Isoenzymes / Q000494:pharmacology*; D008297:Male; D008334:Mandible; D015675:Osteocalcin / Q000494:pharmacology; D010012:Osteogenesis / Q000187:drug effects* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000071681:Tartrate-Resistant Acid Phosphatase; D014945:Wound Healing / Q000187:drug effects*
D005938:Glucocorticoids; D007527:Isoenzymes; D012333:RNA, Messenger; D015675:Osteocalcin; D003907:Dexamethasone; D003094:Collagen; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase