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Int. J. Mol. Sci. 2017, 18(3), 665; doi:10.3390/ijms18030665

Endoplasmic Reticulum Stress and Unfolded Protein Response in Cartilage Pathophysiology; Contributing Factors to Apoptosis and Osteoarthritis

1
Department of Biological Sciences, Boise State University, Boise, ID 83725, USA
2
Biomolecular Sciences Graduate Program, Boise State University, Boise, ID 83725, USA
3
Biomolecular Research Center, Boise State University, Boise, ID 83725, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Charles J. Malemud and Ali Mobasheri
Received: 26 February 2017 / Revised: 15 March 2017 / Accepted: 16 March 2017 / Published: 20 March 2017
(This article belongs to the Special Issue Apoptotic Chondrocytes and Osteoarthritis)
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Abstract

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. View Full-Text
Keywords: chondrocyte; osteoarthritis; endoplasmic reticulum (ER) stress; unfolded protein response; endochondral ossification chondrocyte; osteoarthritis; endoplasmic reticulum (ER) stress; unfolded protein response; endochondral ossification
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Hughes, A.; Oxford, A.E.; Tawara, K.; Jorcyk, C.L.; Oxford, J.T. Endoplasmic Reticulum Stress and Unfolded Protein Response in Cartilage Pathophysiology; Contributing Factors to Apoptosis and Osteoarthritis. Int. J. Mol. Sci. 2017, 18, 665.

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