The Journal of Bone and Joint Surgery (American). 2005;87:1338-1342.
doi:10.2106/JBJS.D.02527
© 2005 The Journal of Bone and Joint Surgery, Inc.
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow CME: Take the exam for this article:
 CME 2: April, May, June 2005
Right arrow [Supplementary Material]
Right arrow Letters to the Editor: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when Letters to the Editor are posted
Right arrow Alert me if a correction is posted
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrowReprints and Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Park, J.-B.
Right arrow Articles by Riew, K. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Park, J.-B.
Right arrow Articles by Riew, K. D.
Related Collections
Right arrow Basic Science
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Technorati  
What's this?

Mitochondrial Involvement in Fas-Mediated Apoptosis of Human Lumbar Disc Cells

Jong-Beom Park, MD, PhD1, Jin-Kyung Lee, MD, PhD2, Sung-Jin Park, MD1, Ki-Won Kim, MD1 and K. Daniel Riew, MD3

1 Department of Orthopaedic Surgery, Uijongbu St. Mary's Hospital, The Catholic University of Korea School of Medicine, 65-1 Kumho-dong, Uijongbu-si, Kyunggi-do, Seoul 480-130, Korea. E-mail address for J.-B. Park: spinepjb{at}catholic.ac.kr
2 Department of Laboratory Medicine, Korea Institute of Radiological and Medical Science, 215-4 Gongneung-dong, Nowon-gu, Seoul 139-709, Korea
3 Cervical Spine Service, Department of Orthopaedic Surgery, Barnes-Jewish Hospital at Washington University School of Medicine, Suite 11300 West Pavilion, St. Louis, MO 63110

Investigation performed at The Catholic University of Korea School of Medicine, Seoul, Korea

Background: Two main pathways of Fas-mediated apoptosis have been identified: the Type-I (death-inducing signaling complex) pathway and the Type-II (mitochondrial) pathway. While apoptotic cell death has been implicated in lumbar degenerative disc disease, we are not aware of any studies in which surgically removed discs from live humans have been examined to determine which of the two pathways is involved in the apoptosis of disc cells. As an initial step in the development of therapies to inhibit inappropriate or premature apoptosis of disc cells, our objective was to determine which pathway is involved.

Methods: We examined thirty-two samples of herniated lumbar disc tissue with use of immunohistochemical staining and Western blot analysis to determine the presence of several proteins, including caspase-8 (associated with the Type-I pathway); BID (BH3 interacting domain death agonist), cytochrome-c, and caspase-9 (associated with the Type-II pathway); and caspase-3 (an executioner of apoptosis). The TUNEL (terminal deoxynucleotidyl transferase [TDT]-mediated dUTP nick end labeling) assay was performed to confirm the occurrence of apoptosis of the disc cells.

Results: The proteins associated with the Type-II pathway (BID, cytochrome-c, and caspase-9) stained positively in all samples. Although the protein associated with the Type-I pathway (caspase-8) was not detected on immunohistochemical analysis, a small amount of caspase-8 was detected on Western blot analysis. However, the expression of Type-II proteins was still higher than the expression of caspase-8 on Western blot analysis. The expression of caspase-3 was identified in all samples with immunohistochemical and Western blot analysis. TUNEL-positive disc cells were identified in all samples.

Conclusions: The results of the present study suggest that human disc cells are Type-II cells, which undergo apoptotic cell death through mitochondrial involvement.

Clinical Relevance: Future therapeutic modalities to inhibit inappropriate or premature apoptotic cell death in degenerating discs should be directed to the mitochondrial pathway.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 JBJSHome page
J.-B. Park, I.-C. Park, S.-J. Park, H.-O. Jin, J.-K. Lee, and K. D. Riew
Anti-Apoptotic Effects of Caspase Inhibitors on Rat Intervertebral Disc Cells
J. Bone Joint Surg. Am., April 1, 2006; 88(4): 771 - 779.
[Abstract] [Full Text] [PDF]