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

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

Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

Sammanfattning

Objective
In this work, we aimed to elucidate the molecular mechanisms driving primary osteoarthritis (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 synovial fluid (SF) samples were obtained from first carpometacarpal (CMC-I) OA and knee joint of OA patients. SF samples were analyzed by label free quantitative mass spectrometry (LC-MSE). Disease-relevant proteins identified in proteomics studies, such as clusterin (CLU), paraoxonase/arylesterase 1 (PON1) and transthyretin (TTR) were validated by enzyme-linked immunosorbent assays (ELISA), and on the mRNA level by droplet digital polymerase chain reaction (ddPCR). Functional studies were performed in vitro using primary chondrocytes.
Results
Differential proteomic changes were observed in the concentration of 40 proteins including CLU, PON1 and transthyretin TTR. Immunoassay analyses of CLU, PON1, TTR, 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 which brings in a new dimension into the pathogenesis of primary OA.
Originalspråkengelska
ArtikelnummerKey232
TidskriftRheumatology
ISSN1462-0324
DOI
Status!!E-pub ahead of print - aug 2018
MoE-publikationstypA1 Tidskriftsartikel-refererad

Vetenskapsgrenar

  • 318 Medicinsk bioteknologi
  • 1182 Biokemi, cell- och molekylärbiologi
  • 3111 Biomedicinska vetenskaper

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title = "Functional analysis of synovial fluid from osteoarthritic knee and carpometacarpal joints unravels different molecular profiles",
abstract = "ObjectiveIn this work, we aimed to elucidate the molecular mechanisms driving primary osteoarthritis (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. MethodsFor this purpose, human synovial fluid (SF) samples were obtained from first carpometacarpal (CMC-I) OA and knee joint of OA patients. SF samples were analyzed by label free quantitative mass spectrometry (LC-MSE). Disease-relevant proteins identified in proteomics studies, such as clusterin (CLU), paraoxonase/arylesterase 1 (PON1) and transthyretin (TTR) were validated by enzyme-linked immunosorbent assays (ELISA), and on the mRNA level by droplet digital polymerase chain reaction (ddPCR). Functional studies were performed in vitro using primary chondrocytes. ResultsDifferential proteomic changes were observed in the concentration of 40 proteins including CLU, PON1 and transthyretin TTR. Immunoassay analyses of CLU, PON1, TTR, 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. ConclusionThis 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 which brings in a new dimension into the pathogenesis of primary OA.",
keywords = "318 Medical biotechnology, OSTEOARTHRITIS, Synovial fluid, 1182 Biochemistry, cell and molecular biology, PROTEOMICS, 3111 Biomedicine",
author = "Goncalo Barreto and Rabah Soliymani and Baumann, {Marc Henrik} and Waris, {Eero Mikko} and Eklund, {Kari K.} and Marcy Zenobi-Wong and Lalowski, {Maciej Maurycy}",
year = "2018",
month = "8",
doi = "10.1093/rheumatology/key232",
language = "English",
journal = "Rheumatology",
issn = "1462-0324",
publisher = "Oxford University Press",

}

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

I: Rheumatology, 08.2018.

Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

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 Henrik

AU - Waris, Eero Mikko

AU - Eklund, Kari K.

AU - Zenobi-Wong , Marcy

AU - Lalowski, Maciej Maurycy

PY - 2018/8

Y1 - 2018/8

N2 - ObjectiveIn this work, we aimed to elucidate the molecular mechanisms driving primary osteoarthritis (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. MethodsFor this purpose, human synovial fluid (SF) samples were obtained from first carpometacarpal (CMC-I) OA and knee joint of OA patients. SF samples were analyzed by label free quantitative mass spectrometry (LC-MSE). Disease-relevant proteins identified in proteomics studies, such as clusterin (CLU), paraoxonase/arylesterase 1 (PON1) and transthyretin (TTR) were validated by enzyme-linked immunosorbent assays (ELISA), and on the mRNA level by droplet digital polymerase chain reaction (ddPCR). Functional studies were performed in vitro using primary chondrocytes. ResultsDifferential proteomic changes were observed in the concentration of 40 proteins including CLU, PON1 and transthyretin TTR. Immunoassay analyses of CLU, PON1, TTR, 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. ConclusionThis 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 which brings in a new dimension into the pathogenesis of primary OA.

AB - ObjectiveIn this work, we aimed to elucidate the molecular mechanisms driving primary osteoarthritis (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. MethodsFor this purpose, human synovial fluid (SF) samples were obtained from first carpometacarpal (CMC-I) OA and knee joint of OA patients. SF samples were analyzed by label free quantitative mass spectrometry (LC-MSE). Disease-relevant proteins identified in proteomics studies, such as clusterin (CLU), paraoxonase/arylesterase 1 (PON1) and transthyretin (TTR) were validated by enzyme-linked immunosorbent assays (ELISA), and on the mRNA level by droplet digital polymerase chain reaction (ddPCR). Functional studies were performed in vitro using primary chondrocytes. ResultsDifferential proteomic changes were observed in the concentration of 40 proteins including CLU, PON1 and transthyretin TTR. Immunoassay analyses of CLU, PON1, TTR, 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. ConclusionThis 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 which brings in a new dimension into the pathogenesis of primary OA.

KW - 318 Medical biotechnology

KW - OSTEOARTHRITIS

KW - Synovial fluid

KW - 1182 Biochemistry, cell and molecular biology

KW - PROTEOMICS

KW - 3111 Biomedicine

U2 - 10.1093/rheumatology/key232

DO - 10.1093/rheumatology/key232

M3 - Article

JO - Rheumatology

JF - Rheumatology

SN - 1462-0324

M1 - Key232

ER -