Autophagy in osteoblasts is involved in mineralization and bone homeostasis

Abstract

Bone remodeling is a tightly controlled mechanism in which osteoblasts (OB), the cells responsible for bone formation, osteoclasts (OC), the cells specialized for bone resorption, and osteocytes, the multifunctional mechanosensing cells embedded in the bone matrix, are the main actors. Increased oxidative stress in OB, the cells producing and mineralizing bone matrix, has been associated with osteoporosis development but the role of autophagy in OB has not yet been addressed. This is the goal of the present study. We first show that the autophagic process is induced in OB during mineralization. Then, using knockdown of autophagy-essential genes and OB-specific autophagy-deficient mice, we demonstrate that autophagy deficiency reduces mineralization capacity. Moreover, our data suggest that autophagic vacuoles could be used as vehicles in OB to secrete apatite crystals. In addition, autophagy-deficient OB exhibit increased oxidative stress and secretion of the receptor activator of NFKB1 (TNFSF11/RANKL), favoring generation of OC, the cells specialized in bone resorption. In vivo, we observed a 50% reduction in trabecular bone mass in OB-specific autophagy-deficient mice. Taken together, our results show for the first time that autophagy in OB is involved both in the mineralization process and in bone homeostasis. These findings are of importance for mineralized tissues which extend from corals to vertebrates and uncover new therapeutic targets for calcified tissue-related metabolic pathologies.

Deferoxamine-Induced Migration and Odontoblast Differentiation via ROS-Dependent Autophagy in Dental Pulp Stem Cells

“…Recently, the role of autophagy in bone physiology and pathophysiology has gradually been unmasked. The effects of autophagy modulators in bone health and osteoblastic differentiation have been widely studied [32], and recent studies have demonstrated that autophagy deficiency compromises osteoblast mineralization in vitro and in vivo [33, 34]. Because bone and dentin share similar components, it is necessary to investigate the role of autophagy in dentin regeneration and odontoblastic differentiation.…”

Osteoporosis and autophagy: What is the relationship?

“…26,27,55 For example, cultures of autophagy gene-knockout osteoblasts (BECN-1, ATG7 e LC3) result in deficiency in the process of mineralization. 56 In vitro studies show that pharmacological inhibition of autophagy in osteoblast-like cells increases oxidative stress and stimulates apoptosis in these cells. In contrast, induction of autophagy in cultures of osteoblast-like cells reduces their oxidative stress and inhibits apoptosis.…”

Involvement of autophagy in tantalum nanoparticle-induced osteoblast proliferation

“…Studies have reported that autophagy can be induced by various nanoparticles in osteoblasts, can promote the differentiation and mineralization of osteoblasts, 36,42 can protect osteoblasts from oxidative damage and apoptosis, 43 and can play essential roles in bone homeostasis. 44 Our present results indicate that Ta-NPs should be added to this nanoparticle list.…”