Magnetic nanoparticle-infiltrated hydroxyapatite scaffolds accelerate osteoclast apoptosis by inhibiting autophagy-aggravated ER stress

Abstract

Since excessive bone resorption conducted by osteoclasts is considered as the leading cause of osteoporosis, particularly for postmenopausal osteoporosis, decreasing the osteoclast number is a potential therapeutic strategy. The present study aims to investigate the effects and underlying mechanisms of magnetic hydroxyapatite (MHA) scaffolds on inhibiting osteoclast proliferation and inducing osteoclast apoptosis simultaneously. Here, a magnetic nanoparticle-infiltrated hydroxyapatite scaffold has an inhibitory effect on osteoclast number via facilitating apoptosis and repressing proliferation, thus reversing the progression of osteoporosis in an ovariectomized rat model. This is mainly attributed to a suitable cellular microenvironment provided by magnetic scaffolds resulting in adequate ATP supply and decreased reactive oxygen species (ROS) level, as well as further inhibiting autophagy. Moreover, the downregulation of autophagy was not sufficient to resist excessive endoplasmic reticulum (ER) stress, resulting in exacerbated cell apoptosis. These studies provided an effective magnetic strategy for reconstructing the balance of osteoblasts and osteoclasts and hold great potential for the clinical management of postmenopausal osteoporosis.