Functional analysis of synovial fluid from osteoarthritic knee and carpometacarpal joints unravels different molecular profiles

Goncalo Barreto, Rabah Soliymani, Marc Baumann, Eero Waris, Kari K. Eklund, Marcy Zenobi-Wong , Maciej Lalowski

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

Kuvaus

Objective. In this work, we aimed to elucidate the molecular mechanisms driving primary OA. By studying the dynamics of protein expression in two different types of OA joints we searched for similarities and disparities to identify key molecular mechanisms driving OA.

Methods. For this purpose, human SF samples were obtained from CMC-I OA and knee joint of OA patients. SF samples were analysed by label-free quantitative liquid chromatography mass spectrometry. Disease-relevant proteins identified in proteomics studies, such as clusterin, paraoxonase/arylesterase 1 (PON1) and transthyretin were validated by enzyme-linked immunosorbent assays, and on the mRNA level by droplet digital PCR. Functional studies were performed in vitro using primary chondrocytes.

Results. Differential proteomic changes were observed in the concentration of 40 proteins including clusterin, PON1 and transthyretin. Immunoassay analyses of clusterin, PON1, transthyretin and other inflammatory cytokines confirmed significant differences in protein concentration in SF of CMC-I and knee OA patients, with primarily lower protein expression levels in CMC-I. Functional studies on chondrocytes unequivocally demonstrated that stimulation with SF obtained from knee OA, in contrast to CMC-I OA joint, caused a significant upregulation in pro-inflammatory response, cell death and hypertrophy.

Conclusion. This study demonstrates that differential expression of molecular players in SF from different OA joints evokes diverse effects on primary chondrocytes. The pathomolecular mechanisms of OA may significantly differ in various joints, a finding that brings a new dimension into the pathogenesis of primary OA.
Alkuperäiskielienglanti
LehtiRheumatology
Vuosikerta58
Numero5
Sivut897-907
Sivumäärä11
ISSN1462-0324
DOI - pysyväislinkit
TilaJulkaistu - toukokuuta 2019
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

Tieteenalat

  • 3111 Biolääketieteet
  • 1182 Biokemia, solu- ja molekyylibiologia
  • 318 Lääketieteen bioteknologia

Lainaa tätä

@article{25c5d43365d94afc913aa4db2c4d21be,
title = "Functional analysis of synovial fluid from osteoarthritic knee and carpometacarpal joints unravels different molecular profiles",
abstract = "Objective. In this work, we aimed to elucidate the molecular mechanisms driving primary OA. By studying the dynamics of protein expression in two different types of OA joints we searched for similarities and disparities to identify key molecular mechanisms driving OA.Methods. For this purpose, human SF samples were obtained from CMC-I OA and knee joint of OA patients. SF samples were analysed by label-free quantitative liquid chromatography mass spectrometry. Disease-relevant proteins identified in proteomics studies, such as clusterin, paraoxonase/arylesterase 1 (PON1) and transthyretin were validated by enzyme-linked immunosorbent assays, and on the mRNA level by droplet digital PCR. Functional studies were performed in vitro using primary chondrocytes.Results. Differential proteomic changes were observed in the concentration of 40 proteins including clusterin, PON1 and transthyretin. Immunoassay analyses of clusterin, PON1, transthyretin and other inflammatory cytokines confirmed significant differences in protein concentration in SF of CMC-I and knee OA patients, with primarily lower protein expression levels in CMC-I. Functional studies on chondrocytes unequivocally demonstrated that stimulation with SF obtained from knee OA, in contrast to CMC-I OA joint, caused a significant upregulation in pro-inflammatory response, cell death and hypertrophy.Conclusion. This study demonstrates that differential expression of molecular players in SF from different OA joints evokes diverse effects on primary chondrocytes. The pathomolecular mechanisms of OA may significantly differ in various joints, a finding that brings a new dimension into the pathogenesis of primary OA.",
keywords = "3111 Biomedicine, 1182 Biochemistry, cell and molecular biology, PROTEOMICS, 318 Medical biotechnology, OSTEOARTHRITIS, Synovial fluid, synovial fluid, label-free protein quantitation, ELISA, inflammation, chondrocytes, osteoarthritis, ARTICULAR-CARTILAGE, EXPRESSION, BIOMARKERS, HIP, PARAOXONASE-1, PROGRESSION, DEPOSITION, CLUSTERIN, DISEASE, MARKERS",
author = "Goncalo Barreto and Rabah Soliymani and Marc Baumann and Eero Waris and Eklund, {Kari K.} and Marcy Zenobi-Wong and Maciej Lalowski",
year = "2019",
month = "5",
doi = "10.1093/rheumatology/key232",
language = "English",
volume = "58",
pages = "897--907",
journal = "Rheumatology",
issn = "1462-0324",
publisher = "Oxford University Press",
number = "5",

}

Functional analysis of synovial fluid from osteoarthritic knee and carpometacarpal joints unravels different molecular profiles. / Barreto, Goncalo; Soliymani, Rabah; Baumann, Marc ; Waris, Eero; Eklund, Kari K.; Zenobi-Wong , Marcy; Lalowski, Maciej .

julkaisussa: Rheumatology, Vuosikerta 58, Nro 5, 05.2019, s. 897-907.

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

TY - JOUR

T1 - Functional analysis of synovial fluid from osteoarthritic knee and carpometacarpal joints unravels different molecular profiles

AU - Barreto, Goncalo

AU - Soliymani, Rabah

AU - Baumann, Marc

AU - Waris, Eero

AU - Eklund, Kari K.

AU - Zenobi-Wong , Marcy

AU - Lalowski, Maciej

PY - 2019/5

Y1 - 2019/5

N2 - Objective. In this work, we aimed to elucidate the molecular mechanisms driving primary OA. By studying the dynamics of protein expression in two different types of OA joints we searched for similarities and disparities to identify key molecular mechanisms driving OA.Methods. For this purpose, human SF samples were obtained from CMC-I OA and knee joint of OA patients. SF samples were analysed by label-free quantitative liquid chromatography mass spectrometry. Disease-relevant proteins identified in proteomics studies, such as clusterin, paraoxonase/arylesterase 1 (PON1) and transthyretin were validated by enzyme-linked immunosorbent assays, and on the mRNA level by droplet digital PCR. Functional studies were performed in vitro using primary chondrocytes.Results. Differential proteomic changes were observed in the concentration of 40 proteins including clusterin, PON1 and transthyretin. Immunoassay analyses of clusterin, PON1, transthyretin and other inflammatory cytokines confirmed significant differences in protein concentration in SF of CMC-I and knee OA patients, with primarily lower protein expression levels in CMC-I. Functional studies on chondrocytes unequivocally demonstrated that stimulation with SF obtained from knee OA, in contrast to CMC-I OA joint, caused a significant upregulation in pro-inflammatory response, cell death and hypertrophy.Conclusion. This study demonstrates that differential expression of molecular players in SF from different OA joints evokes diverse effects on primary chondrocytes. The pathomolecular mechanisms of OA may significantly differ in various joints, a finding that brings a new dimension into the pathogenesis of primary OA.

AB - Objective. In this work, we aimed to elucidate the molecular mechanisms driving primary OA. By studying the dynamics of protein expression in two different types of OA joints we searched for similarities and disparities to identify key molecular mechanisms driving OA.Methods. For this purpose, human SF samples were obtained from CMC-I OA and knee joint of OA patients. SF samples were analysed by label-free quantitative liquid chromatography mass spectrometry. Disease-relevant proteins identified in proteomics studies, such as clusterin, paraoxonase/arylesterase 1 (PON1) and transthyretin were validated by enzyme-linked immunosorbent assays, and on the mRNA level by droplet digital PCR. Functional studies were performed in vitro using primary chondrocytes.Results. Differential proteomic changes were observed in the concentration of 40 proteins including clusterin, PON1 and transthyretin. Immunoassay analyses of clusterin, PON1, transthyretin and other inflammatory cytokines confirmed significant differences in protein concentration in SF of CMC-I and knee OA patients, with primarily lower protein expression levels in CMC-I. Functional studies on chondrocytes unequivocally demonstrated that stimulation with SF obtained from knee OA, in contrast to CMC-I OA joint, caused a significant upregulation in pro-inflammatory response, cell death and hypertrophy.Conclusion. This study demonstrates that differential expression of molecular players in SF from different OA joints evokes diverse effects on primary chondrocytes. The pathomolecular mechanisms of OA may significantly differ in various joints, a finding that brings a new dimension into the pathogenesis of primary OA.

KW - 3111 Biomedicine

KW - 1182 Biochemistry, cell and molecular biology

KW - PROTEOMICS

KW - 318 Medical biotechnology

KW - OSTEOARTHRITIS

KW - Synovial fluid

KW - synovial fluid

KW - label-free protein quantitation

KW - ELISA

KW - inflammation

KW - chondrocytes

KW - osteoarthritis

KW - ARTICULAR-CARTILAGE

KW - EXPRESSION

KW - BIOMARKERS

KW - HIP

KW - PARAOXONASE-1

KW - PROGRESSION

KW - DEPOSITION

KW - CLUSTERIN

KW - DISEASE

KW - MARKERS

U2 - 10.1093/rheumatology/key232

DO - 10.1093/rheumatology/key232

M3 - Article

VL - 58

SP - 897

EP - 907

JO - Rheumatology

JF - Rheumatology

SN - 1462-0324

IS - 5

ER -