Endoplasmic Reticulum Stress and Unfolded Protein Response in Cartilage Pathophysiology; Contributing Factors to Apoptosis and Osteoarthritis.
Chondrocytes of the growth plate undergo apoptosis during the process of endochondral ossification, as well as during the progression of osteoarthritis. Although the regulation of this process is not completely understood, alterations in the precisely orchestrated programmed cell death during development can have catastrophic results, as exemplified by several chondrodystrophies which are frequently accompanied by early onset osteoarthritis. Understanding the mechanisms that underlie chondrocyte apoptosis during endochondral ossification in the growth plate has the potential to impact the development of therapeutic applications for chondrodystrophies and associated early onset osteoarthritis. In recent years, several chondrodysplasias and collagenopathies have been recognized as protein-folding diseases that lead to endoplasmic reticulum stress, endoplasmic reticulum associated degradation, and the unfolded protein response. Under conditions of prolonged endoplasmic reticulum stress in which the protein folding load outweighs the folding capacity of the endoplasmic reticulum, cellular dysfunction and death often occur. However, unfolded protein response (UPR) signaling is also required for the normal maturation of chondrocytes and osteoblasts. Understanding how UPR signaling may contribute to cartilage pathophysiology is an essential step toward therapeutic modulation of skeletal disorders that lead to osteoarthritis.
Department of Biological Sciences, Boise State University, Boise, ID 83725, USA. alexhughes1@u.boisestate.edu.|Biomolecular Research Center, Boise State University, Boise, ID 83725, USA. alexhughes1@u.boisestate.edu.
Alexandria
A
Hughes
Department of Biological Sciences, Boise State University, Boise, ID 83725, USA. aliceoxford@u.boisestate.edu.|Biomolecular Research Center, Boise State University, Boise, ID 83725, USA. aliceoxford@u.boisestate.edu.
Alexandra E
AE
Oxford
Biomolecular Sciences Graduate Program, Boise State University, Boise, ID 83725, USA. kentawara@u.boisestate.edu.|Biomolecular Research Center, Boise State University, Boise, ID 83725, USA. kentawara@u.boisestate.edu.
Ken
K
Tawara
Department of Biological Sciences, Boise State University, Boise, ID 83725, USA. cjorcyk@boisestate.edu.|Biomolecular Sciences Graduate Program, Boise State University, Boise, ID 83725, USA. cjorcyk@boisestate.edu.|Biomolecular Research Center, Boise State University, Boise, ID 83725, USA. cjorcyk@boisestate.edu.
Cheryl L
CL
Jorcyk
Department of Biological Sciences, Boise State University, Boise, ID 83725, USA. joxford@boisestate.edu.|Biomolecular Sciences Graduate Program, Boise State University, Boise, ID 83725, USA. joxford@boisestate.edu.|Biomolecular Research Center, Boise State University, Boise, ID 83725, USA. joxford@boisestate.edu.
Julia Thom
JT
Oxford
D017668:Age of Onset; D000818:Animals; D017209:Apoptosis; D001168:Arthritis / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002113:Calcification, Physiologic; D002356:Cartilage / Q000378:metabolism* / Q000473:pathology*; D019902:Chondrocytes / Q000378:metabolism / Q000473:pathology; D020219:Chondrogenesis; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D003240:Connective Tissue Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress; D006319:Hearing Loss, Sensorineural / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D058990:Molecular Targeted Therapy; D010003:Osteoarthritis / Q000453:epidemiology / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D010006:Osteoblasts / Q000378:metabolism; D012163:Retinal Detachment / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D056811:Unfolded Protein Response
D019485:Bone Morphogenetic Proteins; D003094:Collagen
chondrocyte; endochondral ossification; endoplasmic reticulum (ER) stress; osteoarthritis; unfolded protein response