Advanced glycation end-products downregulating intervertebral disc cell production of proteoglycans in vitro

Kimiaki Yokosuka M.D.1, Jin Soo Park M.D., Ph.D.1, Kotaro Jimbo M.D., Ph.D.1, Kei Yamada M.D., Ph.D.1, Kimiaki Sato M.D., Ph.D.1, Michiyo Tsuru Ph.D.1, Masayoshi Takeuchi Ph.D.1, Sho-Ichi Yamagishi M.D., Ph.D.1, and Kensei Nagata M.D., Ph.D.1
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  • 1 Departments of Orthopedic Surgery and Internal Medicine III, Kurume University School of Medicine, Kurume; and Department of Pathophysiological Science, Faculty of Pharmaceutical Science, Hokuriku University, Kanazawa, Japan
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Object

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.

Abbreviations used in this paper:

AGE = advanced glycation end-product; ECM = extracellular matrix; ELISA = enzyme-linked immunosorbent assay; mRNA = messenger RNA; PCR = polymerase chain reaction; RAGE = AGE receptor; RT = reverse transcriptase.

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Contributor Notes

Address reprint requests to: Jin Soo Park, M.D., Ph.D., Department of Orthopedic Surgery, Kurume University School of Medicine, 67 Asahimachi, Kurume City, Fukuoka 830-0011, Japan. email: jisopark@hotmail.com.
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