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.

Angiotensin (1-7) ameliorates the structural and biochemical alterations of ovariectomy-induced osteoporosis in rats via activation of ACE-2/Mas receptor axis

“…Expressions of different RAS components were reported in the skeletal systems in the current investigation in accordance with other reports 2, 39, 40 . The effector member of RAS (AngII) was found highly expressed together with its forming enzyme, ACE, and receptor (AT1R) in femoral bones heads of OVX osteoporotic animals, which comes in harmony with several studies suggesting the induction of osteoporosis via activation of classical RAS pathway (ACE/AngII/AT1R).…”

Renin inhibitor aliskiren exerts beneficial effect on trabecular bone by regulating skeletal renin-angiotensin system and kallikrein-kinin system in ovariectomized mice

“…Functional studies revealed that Ang II could stimulate the differentiation and activity of osteoclasts in vivo [14] and in vitro [15] and aggravate the loss of bone minerals in rats with osteoporosis induced by estrogen deficiency [14]; furthermore, the AT1R knockout mice showed high bone mass [16]. In addition, we recently demonstrated that the local RAS in bone was involved in age-related osteoporosis of aging mice [17], bone deteriorations of mice with either obstructive nephropathy [18] or type 1 diabetes [19], and others elucidated the involvement of skeletal RAS in the process of fracture healing in a mouse femur fracture model [20] and the steroid-induced osteonecrosis in rabbits [21] as well as the development of postmenopausal osteoporosis in ovariectomized (OVX) animal models [14,22]. Therefore, the emerging evidences demonstrated that the local RAS displays important biological actions in bone tissue.…”

Relationship of α2‐Macroglobulin with Steroid‐Induced Femoral Head Necrosis: A Chinese Population‐Based Association Study in Southeast China

“…Notably, in China, 53.5% of patients with severe acute respiratory syndrome who were prescribed GC developed femoral head osteonecrosis, and SINFH comprises approximately half of non‐traumatic femoral head necrosis. However, the pathogenesis of this disease remains controversial and the various theories explaining SINFH pathogenesis are predominantly classified into the osteoporosis theory, the lipid metabolism disorders theory, the vasculopathy theory, the intraosseous hypertension theory, and the GC cytotoxicity theory.…”