Bi Fanggang, Shi Zhongli, Jiang Shuai, Guo Peng, Yan Shigui
Department of Orthopedic Surgery, the Second Affiliated Hospital, School of Medicine, Zhejiang University, No. 88, Jiefang Road, Hangzhou 310009, China.
Int J Mol Sci. 2014 Sep 29;15(10):17366-79. doi: 10.3390/ijms151017366.
The objective of this study was to investigate whether intermittent administration of parathyroid hormone [1-34] (PTH[1-34]) promotes tendon-bone healing after anterior cruciate ligament (ACL) reconstruction in vivo. A rat model of ACL reconstruction with autograft was established at the left hind leg. Every day, injections of 60 μg PTH[1-34]/kg subcutaneously were given to the PTH group rats (n=10) for four weeks, and the controls (n=10) received saline. The tendon-bone healing process was evaluated by micro-CT, biomechanical test, histological and immunohistochemical analyses. The effects of PTH[1-34] on serum chemistry, bone microarchitecture and expression of the PTH receptor (PTH1R) and osteocalcin were determined. Administration of PTH[1-34] significantly increased serum levels of calcium, alkaline phosphatase (AP), osteocalcin and tartrate-resistant acid phosphatase (TRAP). The expression of PTH1R on both osteocytes and chondrocyte-like cells at the tendon-bone interface was increased in the PTH group. PTH[1-34] also enhanced the thickness and microarchitecture of trabecular bone according to the micro-CT analysis. The results imply that systematically intermittent administration of PTH[1-34] promotes tendon-bone healing at an early stage via up-regulated PTH1R. This method may enable a new strategy for the promotion of tendon-bone healing after ACL reconstruction.
本研究的目的是调查间歇性给予甲状旁腺激素[1-34](PTH[1-34])是否能促进体内前交叉韧带(ACL)重建术后腱骨愈合。在大鼠左后肢建立自体移植ACL重建模型。每天对PTH组大鼠(n = 10)皮下注射60μg PTH[1-34]/kg,持续四周,对照组(n = 10)注射生理盐水。通过显微CT、生物力学测试、组织学和免疫组织化学分析评估腱骨愈合过程。测定PTH[1-34]对血清化学、骨微结构以及甲状旁腺激素受体(PTH1R)和骨钙素表达的影响。给予PTH[1-34]显著提高了血清钙、碱性磷酸酶(AP)、骨钙素和抗酒石酸酸性磷酸酶(TRAP)的水平。PTH组腱骨界面处骨细胞和软骨样细胞上PTH1R的表达增加。根据显微CT分析,PTH[1-34]还增强了小梁骨的厚度和微结构。结果表明,系统性间歇性给予PTH[1-34]通过上调PTH1R在早期促进腱骨愈合。该方法可能为促进ACL重建术后腱骨愈合提供一种新策略。