Alpha‐1 antitrypsin reduces ovariectomy‐induced bone loss in mice

Abstract

Bone loss occurs in menopause due to the decreased estrogen and increased proinflammatory cytokine production. Alpha‐ 1antitrypsin (AAT) is a multifunctional protein with proteinase inhibitor and anti‐inflammatory activities. To determine whether AAT mitigates bone loss induced by estrogen deficiency, thirty‐eight female C57BL/6J mice (7‐wk‐old), were either ovariectomized or sham‐operated. Ovariectomized animals were randomly assigned to AAT‐injected (n=13; 2 mg/mouse, every 3 days for 30 days) or phosphate buffered saline (PBS)‐injected group (n=12), while sham‐operated mice (Sham; n=13) were injected with PBS and used as controls. Ovariectomy resulted in decreased wet uterus weight (P<0.01), bone loss, increased serum leptin concentrations, and higher body weight (P<0.01) compared to sham. AAT treatment increased tibial trabecular bone volume/total volume and trabecular thickness relative to PBS treatment in ovariectomized mice (P<0.01). Ovariectomized mice with AAT‐injection had higher uterus weight (P<0.01), lower serum osteocalcin levels (P<0.05), fewer bone marrow TRAP‐positive osteoclasts (P<0.05) and less expression of calcitonin receptor (P<0.01) in bone than mice injected PBS. These data demonstrate that AAT reduces ovariectomy‐induced bone loss in mice possibly through inhibiting osteoclast activity and bone resorption.