Abstract
Autophagy is an evolutionary conserved and highly regulated recycling process of cellular wastes. Having a housekeeping role, autophagy through the digestion of domestic cytosolic organelles, proteins, macromolecules, and pathogens, eliminates unnecessary materials and provides nutrients and energy for cell survival and maintenance. The critical role of autophagy and autophagy-related proteins in osteoclast differentiation, bone resorption, and maintenance of bone homeostasis has previously been reported. Increasing evidence reveals that autophagy dysregulation leads to alteration of osteoclast function and enhanced bone loss, which is associated with the onset and progression of osteoporosis. In this review, we briefly consolidate the current state-of-the-art technology regarding the role of autophagy in osteoclast function in both physiologic and pathologic conditions to have a more general view on this issue.
Highlights
Bone is a specialized type of connective tissue that holds several important functions including mechanical support of vital organs, locomotion, storage of mineral ions, hormone secretion, modulation of cognition, and anxiety-like behavior that provides the niche site for bone marrow
Arai et al demonstrated that TRAF-mediated Beclin-1 ubiquitination is necessary for RANKL-stimulated osteoclast differentiation, and Beclin-1 knockdown in mice led to the thickening of the cortical bone due to impaired bone resorption [57]
MCPIP induces ROS formation and endoplasmic reticulum stress that causes up-regulation of Beclin-1, lipidation of LC3, and expression of TRAP and cathepsin K [132]. These effects are sequestered by treatment of monocytes with 3-methyladenine and Beclin-1 or Atg7 knockdown, which underlines that osteoclast differentiation by MCPIP is mediated through ROS synthesis and ER stress by leading to autophagy [132]
Summary
Bone is a specialized type of connective tissue that holds several important functions including mechanical support of vital organs, locomotion, storage of mineral ions, hormone secretion, modulation of cognition, and anxiety-like behavior that provides the niche site for bone marrow. Upon attachment to the bone matrix surface by highly dynamic structures called podosomes, osteoclasts become polarized and form a “ruffled border.”. Osteoblasts and osteocytes can regulate osteoclastogenesis since they release M-CSF (macrophage colony stimulating factor), which binds to its receptor c-Fms located on the osteoclast progenitors and induces their proliferation. They release RANKL (Receptor activator of nuclear factor-kappa B ligand) that binds to its receptor RANK expressed on osteoclast precursors and osteoclasts, which regulate the differentiation, survival, and activity of mature osteoclasts [2,7]. This dynamic balance can be influenced by hormones, growth factors, and mechanical impulses as extrinsic factors and autophagy as an intrinsic one [16,25,26]
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