Advanced glycation end-products downregulating intervertebral disc cell production of proteoglycans in vitro.
OBJECTIVE
The authors sought to clarify the role, if any, of advanced glycation end-products (AGEs) in disc degeneration.


METHODS
Intervertebral discs were analyzed for the presence of AGEs and of their receptor (RAGE) by immunohistochemical analysis. Reverse transcriptase polymerase chain reaction (RT-PCR) was performed to detect any RAGE gene expression, and real-time PCR was used to quantify messenger RNA (mRNA) levels of aggrecan and collagen types I and II in nucleus pulposus cells treated with AGEs. Aggrecan protein concentration was determined by enzyme-linked immunosorbent assay. Immunohistochemical analysis revealed that AGEs and RAGE were localized in the nucleus pulposus of the intervertebral disc. Advanced glycation end-products were found to significantly suppress the expression of aggrecan at both mRNA and protein levels in a dose- and time-dependent manner. The levels of collagen types I and II remained unchanged after treatments with AGEs.


CONCLUSIONS
These results suggest that the accumulation of AGEs and their interaction with their receptor in the nucleus pulposus might result in the downregulation of aggrecan production responsible for disc degeneration.
Yokosuka
Kimiaki
K
Department of Orthopedic Surgery and Internal Medicine III, Kurume University School of Medicine, Kurume, Japan.
Park
Jin Soo
JS
Jimbo
Kotaro
K
Yamada
Kei
K
Sato
Kimiaki
K
Tsuru
Michiyo
M
Takeuchi
Masayoshi
M
Yamagishi
Sho-Ichi
S
Nagata
Kensei
K
D000368:Aged; D053674:Aggrecans; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D024022:Fibrillar Collagens / Q000235:genetics / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000502:physiology*; D006801:Humans; D007403:Intervertebral Disc / Q000378:metabolism*; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D008159:Lumbar Vertebrae / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D046509:Tissue Culture Techniques
D053674:Aggrecans; D011508:Chondroitin Sulfate Proteoglycans; D016326:Extracellular Matrix Proteins; D024022:Fibrillar Collagens; D017127:Glycation End Products, Advanced; D037181:Lectins, C-Type; D011509:Proteoglycans; D012333:RNA, Messenger; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic