Boning up on autophagy: the role of autophagy in skeletal biology.
From an evolutionary perspective, the major function of bone is to provide stable sites for muscle attachment and affording protection of vital organs, especially the heart and lungs (ribs) and spinal cord (vertebrae and intervertebral discs). However, bone has a considerable number of other functions: serving as a store for mineral ions, providing a site for blood cell synthesis and participating in a complex system-wide endocrine system. Not surprisingly, bone and cartilage cell homeostasis is tightly controlled, as is the maintenance of tissue structure and mass. While a great deal of new information is accruing concerning skeletal cell homeostasis, one relatively new observation is that the cells of bone (osteoclasts osteoblasts and osteocytes) and cartilage (chondrocytes) exhibit autophagy. The focus of this review is to examine the significance of this process in terms of the functional demands of the skeleton in health and during growth and to provide evidence that dysregulation of the autophagic response is involved in the pathogenesis of diseases of bone (Paget disease of bone) and cartilage (osteoarthritis and the mucopolysaccharidoses). Delineation of molecular changes in the autophagic process is uncovering new approaches for the treatment of diseases that affect the axial and appendicular skeleton.
Jefferson Medical College; Thomas Jefferson University; Philadelphia, PA USA.
Irving M
IM
Shapiro
School of Life Sciences; University of Nottingham Medical School; Nottingham UK.
Robert
R
Layfield
Arthritis Research; The Scripps Research Institute; La Jolla, CA USA.
Martin
M
Lotz
Telethon Institute of Genetics and Medicine (TIGEM); Naples, Italy; Department of Molecular and Human Genetics; Baylor College of Medicine, Houston, TXUSA and Jan and Dan Duncan Neurological Research Institute; Texas Children's Hospital; Houston, TX USA; Medical Genetics; Department of Translational and Medical Science; Federico II University; Naples, Italy.
Carmine
C
Settembre
Department of Medical and Molecular Genetics; Kings College London; London UK.
Caroline
C
Whitehouse
D000818:Animals; D001343:Autophagy; D001847:Bone Diseases / Q000473:pathology / Q000628:therapy; D001842:Bone and Bones / Q000473:pathology*; D002356:Cartilage / Q000254:growth & development; D006801:Humans; D010010:Osteoclasts / Q000473:pathology; D010011:Osteocytes / Q000473:pathology
Paget disease of bone; autophagy; bone; cartilage; chondrocytes; growth plate; mucopolysaccharidosis; osteoarthritis; osteoclasts; remodeling; stem cells