Optical Biomarkers for the Diagnosis of Osteoarthritis through Raman Spectroscopy: Radiological and Biochemical Validation Using Ex Vivo Human Cartilage Samples

Osteoarthritis (OA) is the most common rheumatic disease, characterized by progressive articular cartilage degradation. Raman spectroscopy (RS) has been recently proposed as a label-free tool to detect molecular changes in musculoskeletal tissues. We used cartilage samples derived from human femoral...

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Main Authors: Paula Casal-Beiroa, Vanesa Balboa-Barreiro, Natividad Oreiro, Sonia Pértega-Díaz, Francisco J. Blanco, Joana Magalhães
Format: Article
Language:English
Published: MDPI AG 2021-03-01
Series:Diagnostics
Subjects:
Online Access:https://www.mdpi.com/2075-4418/11/3/546
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author Paula Casal-Beiroa
Vanesa Balboa-Barreiro
Natividad Oreiro
Sonia Pértega-Díaz
Francisco J. Blanco
Joana Magalhães
author_facet Paula Casal-Beiroa
Vanesa Balboa-Barreiro
Natividad Oreiro
Sonia Pértega-Díaz
Francisco J. Blanco
Joana Magalhães
author_sort Paula Casal-Beiroa
collection DOAJ
description Osteoarthritis (OA) is the most common rheumatic disease, characterized by progressive articular cartilage degradation. Raman spectroscopy (RS) has been recently proposed as a label-free tool to detect molecular changes in musculoskeletal tissues. We used cartilage samples derived from human femoral heads to perform an <i>ex vivo</i> study of different Raman signals and ratios, related to major and minor molecular components of articular cartilage, hereby proposed as candidate optical biomarkers for OA. Validation was performed against the radiological Kellgren–Lawrence (K-L) grading system, as a gold standard, and cross-validated against sulfated glycosaminoglycans (sGAGs) and total collagens (<i>Hyp</i>) biochemical contents. Our results showed a significant decrease in sGAGs (SGAGs, A1063 cm<sup>−1</sup>/A1004 cm<sup>−1</sup>) and proteoglycans (PGs, A1375 cm<sup>−1</sup>/A1004 cm<sup>−1</sup>) and a significant increase in collagen disorganization (ColD/F, A1245 cm<sup>−1</sup>/A1270 cm<sup>−1</sup>), with OA severity. These were correlated with sGAGs or Hyp contents, respectively. Moreover, the SGAGs/HA ratio (A1063 cm<sup>−1</sup>/A960 cm<sup>−1</sup>), representing a functional matrix, rich in proteoglycans, to a mineralized matrix-hydroxyapatite (HA), was significantly lower in OA cartilage (K-L I vs. III–IV, <i>p</i> < 0.05), whilst the mineralized to collagenous matrix ratio (HA/Col, A960 cm<sup>−1</sup>/A920 cm<sup>−1</sup>) increased, being correlated with K-L. OA samples showed signs of tissue mineralization, supported by the presence of calcium crystals-related signals, such as phosphate, carbonate, and calcium pyrophosphate dihydrate (MGP, A960 cm<sup>−1</sup>/A1004 cm<sup>−1</sup>, MGC, A1070 cm<sup>−1</sup>/A1004 cm<sup>−1</sup> and A1050 cm<sup>−1</sup>/A1004 cm<sup>−1</sup>). Finally, we observed an increase in lipids ratio (IL, A1450 cm<sup>−1</sup>/A1670 cm<sup>−1</sup>) with OA severity. As a conclusion, we have described the molecular fingerprint of hip cartilage, validating a panel of optical biomarkers and the potential of RS as a complementary diagnostic tool for OA.
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spelling doaj.art-55320df20ba84597b8d1b8fa698778872023-11-21T11:06:28ZengMDPI AGDiagnostics2075-44182021-03-0111354610.3390/diagnostics11030546Optical Biomarkers for the Diagnosis of Osteoarthritis through Raman Spectroscopy: Radiological and Biochemical Validation Using Ex Vivo Human Cartilage SamplesPaula Casal-Beiroa0Vanesa Balboa-Barreiro1Natividad Oreiro2Sonia Pértega-Díaz3Francisco J. Blanco4Joana Magalhães5Unidad de Medicina Regenerativa, Grupo de Investigación de Reumatología (GIR), Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), SERGAS, Universidade da Coruña (UDC), C/As Xubias de Arriba 84, 15006 A Coruña, SpainUnidad de Epidemiología Clínica e Investigación Bioestadística, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), SERGAS, Universidade da Coruña (UDC), C/As Xubias de Arriba 84, 15006 A Coruña, SpainUnidad de Medicina Regenerativa, Grupo de Investigación de Reumatología (GIR), Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), SERGAS, Universidade da Coruña (UDC), C/As Xubias de Arriba 84, 15006 A Coruña, SpainUnidad de Epidemiología Clínica e Investigación Bioestadística, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), SERGAS, Universidade da Coruña (UDC), C/As Xubias de Arriba 84, 15006 A Coruña, SpainUnidad de Medicina Regenerativa, Grupo de Investigación de Reumatología (GIR), Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), SERGAS, Universidade da Coruña (UDC), C/As Xubias de Arriba 84, 15006 A Coruña, SpainUnidad de Medicina Regenerativa, Grupo de Investigación de Reumatología (GIR), Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), SERGAS, Universidade da Coruña (UDC), C/As Xubias de Arriba 84, 15006 A Coruña, SpainOsteoarthritis (OA) is the most common rheumatic disease, characterized by progressive articular cartilage degradation. Raman spectroscopy (RS) has been recently proposed as a label-free tool to detect molecular changes in musculoskeletal tissues. We used cartilage samples derived from human femoral heads to perform an <i>ex vivo</i> study of different Raman signals and ratios, related to major and minor molecular components of articular cartilage, hereby proposed as candidate optical biomarkers for OA. Validation was performed against the radiological Kellgren–Lawrence (K-L) grading system, as a gold standard, and cross-validated against sulfated glycosaminoglycans (sGAGs) and total collagens (<i>Hyp</i>) biochemical contents. Our results showed a significant decrease in sGAGs (SGAGs, A1063 cm<sup>−1</sup>/A1004 cm<sup>−1</sup>) and proteoglycans (PGs, A1375 cm<sup>−1</sup>/A1004 cm<sup>−1</sup>) and a significant increase in collagen disorganization (ColD/F, A1245 cm<sup>−1</sup>/A1270 cm<sup>−1</sup>), with OA severity. These were correlated with sGAGs or Hyp contents, respectively. Moreover, the SGAGs/HA ratio (A1063 cm<sup>−1</sup>/A960 cm<sup>−1</sup>), representing a functional matrix, rich in proteoglycans, to a mineralized matrix-hydroxyapatite (HA), was significantly lower in OA cartilage (K-L I vs. III–IV, <i>p</i> < 0.05), whilst the mineralized to collagenous matrix ratio (HA/Col, A960 cm<sup>−1</sup>/A920 cm<sup>−1</sup>) increased, being correlated with K-L. OA samples showed signs of tissue mineralization, supported by the presence of calcium crystals-related signals, such as phosphate, carbonate, and calcium pyrophosphate dihydrate (MGP, A960 cm<sup>−1</sup>/A1004 cm<sup>−1</sup>, MGC, A1070 cm<sup>−1</sup>/A1004 cm<sup>−1</sup> and A1050 cm<sup>−1</sup>/A1004 cm<sup>−1</sup>). Finally, we observed an increase in lipids ratio (IL, A1450 cm<sup>−1</sup>/A1670 cm<sup>−1</sup>) with OA severity. As a conclusion, we have described the molecular fingerprint of hip cartilage, validating a panel of optical biomarkers and the potential of RS as a complementary diagnostic tool for OA.https://www.mdpi.com/2075-4418/11/3/546optical biomarkersosteoarthritisK-L gradeglycosaminoglycanstotal collagenlipids
spellingShingle Paula Casal-Beiroa
Vanesa Balboa-Barreiro
Natividad Oreiro
Sonia Pértega-Díaz
Francisco J. Blanco
Joana Magalhães
Optical Biomarkers for the Diagnosis of Osteoarthritis through Raman Spectroscopy: Radiological and Biochemical Validation Using Ex Vivo Human Cartilage Samples
Diagnostics
optical biomarkers
osteoarthritis
K-L grade
glycosaminoglycans
total collagen
lipids
title Optical Biomarkers for the Diagnosis of Osteoarthritis through Raman Spectroscopy: Radiological and Biochemical Validation Using Ex Vivo Human Cartilage Samples
title_full Optical Biomarkers for the Diagnosis of Osteoarthritis through Raman Spectroscopy: Radiological and Biochemical Validation Using Ex Vivo Human Cartilage Samples
title_fullStr Optical Biomarkers for the Diagnosis of Osteoarthritis through Raman Spectroscopy: Radiological and Biochemical Validation Using Ex Vivo Human Cartilage Samples
title_full_unstemmed Optical Biomarkers for the Diagnosis of Osteoarthritis through Raman Spectroscopy: Radiological and Biochemical Validation Using Ex Vivo Human Cartilage Samples
title_short Optical Biomarkers for the Diagnosis of Osteoarthritis through Raman Spectroscopy: Radiological and Biochemical Validation Using Ex Vivo Human Cartilage Samples
title_sort optical biomarkers for the diagnosis of osteoarthritis through raman spectroscopy radiological and biochemical validation using ex vivo human cartilage samples
topic optical biomarkers
osteoarthritis
K-L grade
glycosaminoglycans
total collagen
lipids
url https://www.mdpi.com/2075-4418/11/3/546
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