Autophagy: a key pathway of TNF-induced inflammatory bone loss

Abstract

Autophagy describes the degradation of unnecessary or dysfunctional cellular components through the lysosomal machinery. Autophagy is essentially required to prevent accumulation of cellular damage and to ensure cellular homeostasis. Indeed, impaired autophagy has been implicated in a variety of different diseases. We examined the role of autophagy in inflammatory bone loss. We demonstrated that autophagy is activated by the pro-inflammatory cytokine tumor necrosis factor (TNF/TNFα) in osteoclasts of patients with rheumatoid arthritis (RA). Autophagy induces osteoclast differentiation and stimulates osteoclast-mediated bone resorption in vitro and in vivo, thereby highlighting autophagy as a novel mediator of TNF-induced bone resorption.

Keywords: TNFα; arthritis; autophagy; bone resorption; osteoclasts.

Figure 1. Proposed model of autophagy in the pathogenesis of rheumatoid arthritis and associated bone loss. The stimulatory effects of TNF on autophagy and the crucial role of autophagy for osteoclastogenesis drive the bone erosion in TNF tg mice.