Autophagy in bone homeostasis and the onset of osteoporosis

Abstract

Autophagy is an evolutionarily conserved intracellular process, in which domestic cellular components are selectively digested for the recycling of nutrients and energy. This process is indispensable for cell homeostasis maintenance and stress responses. Both genetic and functional studies have demonstrated that multiple proteins involved in autophagic activities are critical to the survival, differentiation, and functioning of bone cells, including osteoblasts, osteocytes, and osteoclasts. Dysregulation at the level of autophagic activity consequently disturbs the balance between bone formation and bone resorption and mediates the onset and progression of multiple bone diseases, including osteoporosis. This review aims to introduce the topic of autophagy, summarize the understanding of its relevance in bone physiology, and discuss its role in the onset of osteoporosis and therapeutic potential.

Keywords: Bone; Osteoporosis.

Fig. 1

Three types of autophagy. Schematic illustrations of (a) macroautophagy, (b) chaperone-mediated autophagy, and (c) microautophagy

Fig. 2

Major stages in the autophagic process. Schematic illustrations of major stages in the autophagic process: initiation and nucleation, elongation, closure and maturation, fusion and degradation

Fig. 3

Non-selective and selective autophagy. Schematic illustrations of starvation-induced nonselective autophagy and target-specific selective autophagy

Fig. 4

Bone remodeling and skeletal system homeostasis. Osteoblasts, osteocytes, and osteoclasts are tightly linked to regulate bone remodeling and orchestrate the homeostasis of the skeletal system

Fig. 5

Autophagy and the functioning of three types of bone cells. Autophagy maintains the homeostasis of osteoblasts, osteoclasts, and osteocytes

Fig. 6

Signal pathways regulating the bone-related autophagic activity. mTOR and ULK1 serve as pivots in conducting stress signals and growth factors to downstream autophagy-related proteins

Fig. 7

Pathological malfunction of autophagy triggers the onset of osteoporosis. Aging, estrogen deficiency, and glucocorticoids downregulate autophagic activity and thus lead to osteoporosis