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Identification of potential prognostic markers for knee osteoarthritis by serum proteomic analysis.

Takinami Y, Yoshimatsu S, Uchiumi T, Toyosaki-Maeda T, Morita A, Ishihara T, Yamane S, Fukuda I, Okamoto H, Numata Y, Fukui N - Biomark Insights (2013)

Bottom Line: Subsequent analyses indicated that these peaks corresponded to apolipoprotein C-I, C-III, and an N-terminal truncated form of transthyretin, respectively.Three potential biomarkers were identified whose serum levels differed significantly between OA progressors and nonprogressors.These biomarkers are expected to be prognostic biomarkers for knee OA and to facilitate the development of novel disease-modifying treatments for OA.

View Article: PubMed Central - PubMed

Affiliation: Shionogi Pharmaceutical Research Center, Shionogi and Co., Ltd., Osaka, Japan.

ABSTRACT

Background: As osteoarthritis (OA) is a highly heterogeneous disease in terms of progression, establishment of prognostic biomarkers would be highly beneficial for treatment. The present study was performed to identify novel biomarkers capable of predicting the progression of knee OA.

Methods: A total of 69 plasma samples (OA patients undergoing radiographic progression, n = 25; nonprogression, n = 33; healthy donors, n = 11) were analyzed by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS), and ion peaks of interest were identified by liquid chromatography and matrix-assisted laser desorption/ionization (MALDI)-TOF MS. The identities of these proteins were further validated by immunoprecipitation combined with SELDI-TOF MS analysis.

Results: SELDI-TOF MS analysis indicated that the intensities of 3 ion peaks differed significantly between progressors and nonprogressors. Subsequent analyses indicated that these peaks corresponded to apolipoprotein C-I, C-III, and an N-terminal truncated form of transthyretin, respectively. The identities of these proteins were confirmed by the loss of ion peaks in SELDI-TOF MS spectra by immunoprecipitation using specific antibodies for the respective proteins.

Conclusions: Three potential biomarkers were identified whose serum levels differed significantly between OA progressors and nonprogressors. These biomarkers are expected to be prognostic biomarkers for knee OA and to facilitate the development of novel disease-modifying treatments for OA.

No MeSH data available.


Related in: MedlinePlus

Results of SELDI-TOF MS analysis. Representative results of plasma samples from healthy donors (Control), nonprogressors, and progressors are shown for each of fraction 2 (Fr. 2) with CM10 (A), fraction 4 (Fr. 4) with H50 (B), and fraction 6 (Fr. 6) with H50 (C). Arrows indicate the peaks with significantly different intensities between progressors and nonprogressors, which were designated as peak 1 (A), 2 (B), and 3 (C), respectively. The m/z values for these peaks are shown.
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f2-bmi-8-2013-085: Results of SELDI-TOF MS analysis. Representative results of plasma samples from healthy donors (Control), nonprogressors, and progressors are shown for each of fraction 2 (Fr. 2) with CM10 (A), fraction 4 (Fr. 4) with H50 (B), and fraction 6 (Fr. 6) with H50 (C). Arrows indicate the peaks with significantly different intensities between progressors and nonprogressors, which were designated as peak 1 (A), 2 (B), and 3 (C), respectively. The m/z values for these peaks are shown.

Mentions: From the results of SELDI-TOF MS analysis, 3 ion peaks were found to exhibit significantly different peak intensities between the samples from the progressors and those from the nonprogressors. These peaks were observed at m/z 5079 of fraction 2 treated with CM10 (peak 1) (Fig. 2A), at m/z 6432 of fraction 4 with H50 (peak 2) (Fig. 2B), and at m/z 9017 of fraction 6 with H50 (peak 3) (Fig. 2C). For peaks 1 and 2, the peak intensities were significantly higher in the progressors compared with the nonprogressors (Fig. 3A and B), while the intensity of peak 3 was significantly lower in the progressors than the non-progressors (Fig. 3C). Among these 3 peaks, peak 3 showed the most obvious difference between the progressors and nonprogressors (P = 0.002, Mann-Whitney U test).


Identification of potential prognostic markers for knee osteoarthritis by serum proteomic analysis.

Takinami Y, Yoshimatsu S, Uchiumi T, Toyosaki-Maeda T, Morita A, Ishihara T, Yamane S, Fukuda I, Okamoto H, Numata Y, Fukui N - Biomark Insights (2013)

Results of SELDI-TOF MS analysis. Representative results of plasma samples from healthy donors (Control), nonprogressors, and progressors are shown for each of fraction 2 (Fr. 2) with CM10 (A), fraction 4 (Fr. 4) with H50 (B), and fraction 6 (Fr. 6) with H50 (C). Arrows indicate the peaks with significantly different intensities between progressors and nonprogressors, which were designated as peak 1 (A), 2 (B), and 3 (C), respectively. The m/z values for these peaks are shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3735238&req=5

f2-bmi-8-2013-085: Results of SELDI-TOF MS analysis. Representative results of plasma samples from healthy donors (Control), nonprogressors, and progressors are shown for each of fraction 2 (Fr. 2) with CM10 (A), fraction 4 (Fr. 4) with H50 (B), and fraction 6 (Fr. 6) with H50 (C). Arrows indicate the peaks with significantly different intensities between progressors and nonprogressors, which were designated as peak 1 (A), 2 (B), and 3 (C), respectively. The m/z values for these peaks are shown.
Mentions: From the results of SELDI-TOF MS analysis, 3 ion peaks were found to exhibit significantly different peak intensities between the samples from the progressors and those from the nonprogressors. These peaks were observed at m/z 5079 of fraction 2 treated with CM10 (peak 1) (Fig. 2A), at m/z 6432 of fraction 4 with H50 (peak 2) (Fig. 2B), and at m/z 9017 of fraction 6 with H50 (peak 3) (Fig. 2C). For peaks 1 and 2, the peak intensities were significantly higher in the progressors compared with the nonprogressors (Fig. 3A and B), while the intensity of peak 3 was significantly lower in the progressors than the non-progressors (Fig. 3C). Among these 3 peaks, peak 3 showed the most obvious difference between the progressors and nonprogressors (P = 0.002, Mann-Whitney U test).

Bottom Line: Subsequent analyses indicated that these peaks corresponded to apolipoprotein C-I, C-III, and an N-terminal truncated form of transthyretin, respectively.Three potential biomarkers were identified whose serum levels differed significantly between OA progressors and nonprogressors.These biomarkers are expected to be prognostic biomarkers for knee OA and to facilitate the development of novel disease-modifying treatments for OA.

View Article: PubMed Central - PubMed

Affiliation: Shionogi Pharmaceutical Research Center, Shionogi and Co., Ltd., Osaka, Japan.

ABSTRACT

Background: As osteoarthritis (OA) is a highly heterogeneous disease in terms of progression, establishment of prognostic biomarkers would be highly beneficial for treatment. The present study was performed to identify novel biomarkers capable of predicting the progression of knee OA.

Methods: A total of 69 plasma samples (OA patients undergoing radiographic progression, n = 25; nonprogression, n = 33; healthy donors, n = 11) were analyzed by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS), and ion peaks of interest were identified by liquid chromatography and matrix-assisted laser desorption/ionization (MALDI)-TOF MS. The identities of these proteins were further validated by immunoprecipitation combined with SELDI-TOF MS analysis.

Results: SELDI-TOF MS analysis indicated that the intensities of 3 ion peaks differed significantly between progressors and nonprogressors. Subsequent analyses indicated that these peaks corresponded to apolipoprotein C-I, C-III, and an N-terminal truncated form of transthyretin, respectively. The identities of these proteins were confirmed by the loss of ion peaks in SELDI-TOF MS spectra by immunoprecipitation using specific antibodies for the respective proteins.

Conclusions: Three potential biomarkers were identified whose serum levels differed significantly between OA progressors and nonprogressors. These biomarkers are expected to be prognostic biomarkers for knee OA and to facilitate the development of novel disease-modifying treatments for OA.

No MeSH data available.


Related in: MedlinePlus