Role of the local bone renin-angiotensin system in steroid-induced osteonecrosis in rabbits

Abstract

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.