Avian bone metabolism diseases affect the development and production of chickens, and many of these diseases can be prevented and controlled by balanced nutrition and hormone medicine. The steroid hormone 1 alpha,25-dihydroxyvitamin D-3 plays a key role in maintaining the balance of avian bone metabolism. Clinically, 1 alpha,25-(OH)(2)D-3 has been used to treat several bone diseases. Although several previous studies have investigated the effects of 1 alpha,25-(OH)(2)D-3 on osteoclastogenesis, the mechanisms underpinning osteoclast (OC) activity remain largely unknown. Herein, we used molecular and cell biology approaches to demonstrate that 1 alpha,25-(OH)(2)D-3 increases avian OC formation and activity, and upregulates bone resorption-related genes. Moreover, 1 alpha,25-(OH)(2)D-3 regulates the OC cytoskeleton by increasing the formation of zipper-like structure in OC precursor cells to potentiate OC activity via the Src/Racl signaling pathway. These findings provide new insight into the role of 1 alpha,25-(OH)(2)D-3 in OC activity. (C) 2018 Elsevier Inc. All rights reserved.