Li Yan, Tan Yinghui, Zhang Gang, Yang Bo, Zhang Jianshe
Department of Oral and Maxillofacial Surgery, Xingqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China.
J Oral Maxillofac Surg. 2009 Feb;67(2):273-9. doi: 10.1016/j.joms.2008.06.077.
Previous studies have found that calcitonin gene-related peptide (CGRP) takes part in the local regulation of bone growth and metabolism. However, the detailed regulatory mechanism of CGRP in the bone healing has not been explored. The objective of this study was to investigate the effects and the regulatory mechanism of CGRP on the expression and activity of nitric oxide synthase (NOS) in bony callus during mandibular defect healing.
To determine the effect of CGRP on bony callus, a bone defect in the left mandible was created in 48 adult rabbits (divided randomly into experimental and control group) and half of them underwent inferior alveolar nerve amputation. The bony callus were collected 4, 7, 14, and 28 days after operation, and the expressions of CGRP and NOS in the paraffin slices were analyzed with immunohistochemical staining. The activity of calcium-dependent nitric oxide synthase (cNOS) and inducible nitric oxide synthase (iNOS) in the fresh specimens were measured with the NOS detecting kit.
In the immunohistochemical analysis of bony callus, the immunohistochemical stain of CGRP was lower in experimental groups than in control groups from 4 to 14 days (P< .05 or P< .01), and the stain of eNOS showed the same phenomena from 4 to 7 days (P< .01), but the stain of iNOS did not show any statistical difference. In the NOS activity analysis, the activity of cNOS was lower in experimental groups than in control groups from 4 to 7 days (P< .05 or P< .01), and the activity of iNOS was lower in experimental groups than in control groups from 7 to 14 days (P< .01).
The expression and activity of NOS has a positive correlation with CGRP expression during bone healing. CGRP may promote fracture healing via regulating the expression and the activity of NOS.
以往研究发现降钙素基因相关肽(CGRP)参与骨生长和代谢的局部调节。然而,CGRP在骨愈合中的详细调节机制尚未得到探索。本研究的目的是探讨CGRP对下颌骨缺损愈合过程中骨痂中一氧化氮合酶(NOS)表达和活性的影响及其调节机制。
为确定CGRP对骨痂的影响,在48只成年兔的左下颌骨制造骨缺损(随机分为实验组和对照组),其中一半进行下牙槽神经切断术。术后4、7、14和28天收集骨痂,用免疫组织化学染色分析石蜡切片中CGRP和NOS的表达。用NOS检测试剂盒测定新鲜标本中钙依赖性一氧化氮合酶(cNOS)和诱导型一氧化氮合酶(iNOS)的活性。
在骨痂的免疫组织化学分析中,实验组CGRP的免疫组织化学染色在4至14天低于对照组(P<0.05或P<0.01),eNOS染色在4至7天呈现相同现象(P<0.01),但iNOS染色无统计学差异。在NOS活性分析中,实验组cNOS活性在4至7天低于对照组(P<0.05或P<0.01),实验组iNOS活性在7至14天低于对照组(P<0.01)。
骨愈合过程中NOS的表达和活性与CGRP表达呈正相关。CGRP可能通过调节NOS的表达和活性促进骨折愈合。