Autophagy as a target for glucocorticoid-induced osteoporosis therapy

Abstract

Autophagy takes part in regulating the eukaryotic cells function and the progression of numerous diseases, but its clinical utility has not been fully developed yet. Recently, mounting evidences highlight an important correlation between autophagy and bone homeostasis, mediated by osteoclasts, osteocytes, bone marrow mesenchymal stem cells, and osteoblasts, and autophagy plays a vital role in the pathogenesis of glucocorticoid-induced osteoporosis (GIOP). The combinations of autophagy activators/inhibitors with anti-GIOP first-line drugs or some new autophagy-based manipulators, such as regulation of B cell lymphoma 2 family proteins and caspase-dependent clearance of autophagy-related gene proteins, are likely to be the promising approaches for GIOP clinical treatments. In view of the important role of autophagy in the pathogenesis of GIOP, here we review the potential mechanisms about the impacts of autophagy in GIOP and its association with GIOP therapy.

Keywords: Apoptosis; Autophagy; Bone metabolic diseases; Glucocorticoid-induced osteoporosis; Review; Therapeutic target.

Fig. 1

The steps of autophagy. This process includes initiation, nucleation, expansion of isolation membrane, fusion, and degradation. And numerous molecules (such as ATGs, Beclin-1, and LC3) and signaling pathways (like mTORC1 pathway and PI3K pathway)

Fig. 2

Physiopathology of GIOP. GCs induce decreased bone mass, impaired bone microstructure, decreased bone strength, and increased fracture risk through regulating the function of BMSCs, osteoblasts, osteoclasts, and osteocytes

Fig. 3

The functions of autophagy in the pathogenesis of GIOP. The activation or inhibition of autophagy participates in the maintaining of bone homeostasis, which is mediated by BMSCs, osteoblasts, osteoclasts, and osteocytes

Fig. 4

Potential therapeutic targets for GIOP on autophagy. The combinations of autophagy activators/inhibitors with some first-line drugs, as well as novel autophagy-based manipulations, including Bcl-2 family regulation and caspase-dependent cleavage of ATG proteins are likely to be the promising approaches for GIOP clinical treatments