Zhang Yongtao, Wang Kunzheng, Song Qichun, Liu Ruiyu, Ji Wenchen, Ji Le, Wang Chunsheng
Department of Orthopaedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Mol Med Rep. 2014 Apr;9(4):1128-34. doi: 10.3892/mmr.2014.1978. Epub 2014 Feb 21.
The specific pathogenesis of steroid‑induced osteonecrosis (ON) is yet to be elucidated and until recently effective prophylactic therapies have not been available. The local renin‑angiotensin system (RAS) exists in the bone and has an important role in local bone regulation. However, to the best of our knowledge, the interrelation between local bone RAS and steroid‑induced ON is yet to be investigated. In the present study, 45 rabbits were injected with a single intramuscular dose of 20 mg/kg methylprednisolone acetate (MPA) and were sacrificed 1 (group A), 2 (group B) and 3 (group C) weeks subsequent to MPA administration (n=15 per group). Ten rabbits were used as a control group (group N). The presence or absence of ON in the bilateral femoral heads was examined histopathologically. The mRNA and protein expression of components of the RAS, including angiotensin II (Ang II), angiotensin converting enzyme (ACE) and Ang II type 1 (AT1) and Ang II type 2 (AT2) receptors, were detected in the bone. Significant changes in Ang II, ACE, and AT1 and AT2 receptor expression were observed in the bone of the rabbits in the different groups. Moreover, the expression of Ang II and ACE was highest one week subsequent to administration of the glucocorticoid methylprednisolone and the expression of the AT1 and AT2 receptors was highest two weeks following methylprednisolone administration. ON occurs most significantly at three weeks following the administration of MPA in this animal model, thus the changes in Ang II, ACE and AT1 and AT2 receptor expression preceded this. The present study found that ON was strongly associated with the activation of the local bone RAS in rabbits.
类固醇诱导性骨坏死（ON）的具体发病机制尚未阐明，直到最近仍没有有效的预防性治疗方法。局部肾素-血管紧张素系统（RAS）存在于骨骼中，在局部骨调节中起重要作用。然而，据我们所知，局部骨RAS与类固醇诱导性ON之间的相互关系尚未得到研究。在本研究中，给45只兔子单次肌内注射20mg/kg醋酸甲泼尼龙（MPA），并在MPA给药后1周（A组）、2周（B组）和3周（C组）处死（每组n = 15）。10只兔子作为对照组（N组）。通过组织病理学检查双侧股骨头是否存在ON。检测骨骼中RAS成分的mRNA和蛋白表达，包括血管紧张素II（Ang II）、血管紧张素转换酶（ACE）以及Ang II 1型（AT1）和2型（AT2）受体。在不同组兔子的骨骼中观察到Ang II、ACE以及AT1和AT2受体表达的显著变化。此外，糖皮质激素甲泼尼龙给药后1周Ang II和ACE的表达最高，甲泼尼龙给药后2周AT1和AT2受体的表达最高。在该动物模型中，MPA给药后3周ON最为明显，因此Ang II、ACE以及AT1和AT2受体表达的变化先于此发生。本研究发现，在兔子中ON与局部骨RAS的激活密切相关。
