PMID- 36233118
OWN - NLM
STAT- MEDLINE
DCOM- 20221017
LR  - 20221019
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 23
IP  - 19
DP  - 2022 Oct 5
TI  - Inflammation-Driven Secretion Potential Is Upregulated in Osteoarthritic 
      Fibroblast-Like Synoviocytes.
LID - 10.3390/ijms231911817 [doi]
LID - 11817
AB  - Osteoarthritis (OA) is one of the most common joint pathologies and a major cause 
      of disability among the population of developed countries. It manifests as a 
      gradual degeneration of the cartilage and subchondral part of the bone, leading 
      to joint damage. Recent studies indicate that not only the cells that make up the 
      articular cartilage but also the synoviocytes, which build the membrane 
      surrounding the joint, contribute to the development of OA. Therefore, the aim of 
      the study was to determine the response to inflammatory factors of osteoarthritic 
      synoviocytes and to identify proteins secreted by them that may influence the 
      progression of OA. This study demonstrated that fibroblast-like synoviocytes of 
      OA patients (FLS-OA) respond more strongly to pro-inflammatory stimulation than 
      cells obtained from control patients (FLS). These changes were observed at the 
      transcriptome level and subsequently confirmed by protein analysis. FLS-OA 
      stimulated by pro-inflammatory factors [such as lipopolysaccharide (LPS) and 
      tumor necrosis factor alpha (TNFalpha) were shown to secrete significantly more 
      chemokines (CXCL6, CXCL10, and CXCL16) and growth factors [angiopoietin-like 
      protein 1 (ANGPTL1), fibroblast growth factor 5 (FGF5), and insulin-like growth 
      factor 2 (IGF2)] than control cells. Moreover, the translation of proteolytic 
      enzymes [matrix metalloprotease 3 (MMP3), cathepsin K (CTSK), and cathepsin S 
      (CTSS)] by FLS-OA is increased under inflammatory conditions. Our data indicate 
      that the FLS of OA patients are functionally altered, resulting in an enhanced 
      response to the presence of pro-inflammatory factors in the environment, 
      manifested by the increased production of the previously mentioned proteins, 
      which may promote further disease progression.
FAU - Chwastek, Jakub
AU  - Chwastek J
AD  - Department of Neurochemistry, Maj Institute of Pharmacology Polish Academy of 
      Sciences, 31-343 Krakow, Poland.
FAU - Kedziora, Marta
AU  - Kedziora M
AUID- ORCID: 0000-0002-6980-8273
AD  - Department of Neurochemistry, Maj Institute of Pharmacology Polish Academy of 
      Sciences, 31-343 Krakow, Poland.
FAU - Borczyk, Malgorzata
AU  - Borczyk M
AD  - Laboratory of Pharmacogenomics, Department of Molecular Pharmacology, Maj 
      Institute of Pharmacology Polish Academy of Sciences, 31-343 Krakow, Poland.
FAU - Korostynski, Michal
AU  - Korostynski M
AUID- ORCID: 0000-0002-4273-7401
AD  - Laboratory of Pharmacogenomics, Department of Molecular Pharmacology, Maj 
      Institute of Pharmacology Polish Academy of Sciences, 31-343 Krakow, Poland.
FAU - Starowicz, Katarzyna
AU  - Starowicz K
AUID- ORCID: 0000-0003-0091-0066
AD  - Department of Neurochemistry, Maj Institute of Pharmacology Polish Academy of 
      Sciences, 31-343 Krakow, Poland.
LA  - eng
GR  - 2016/23/B/NZ7/01143/National Science Center/
GR  - Statutory funds/Maj Institute of Pharmacology/
PT  - Journal Article
DEP - 20221005
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Somatomedins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 129653-64-1 (Fibroblast Growth Factor 5)
RN  - EC 3.4.22.38 (Cathepsin K)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Cathepsin K/metabolism
MH  - Cells, Cultured
MH  - Fibroblast Growth Factor 5/metabolism
MH  - Fibroblasts/metabolism
MH  - Humans
MH  - Inflammation/pathology
MH  - Lipopolysaccharides/metabolism
MH  - Matrix Metalloproteinase 3/metabolism
MH  - *Osteoarthritis/metabolism
MH  - *Somatomedins/metabolism
MH  - Synovial Membrane/pathology
MH  - *Synoviocytes/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
PMC - PMC9570304
OTO - NOTNLM
OT  - RNA-seq
OT  - chemokines
OT  - fibroblast-like synoviocytes
OT  - inflammation
OT  - osteoarthritis
COIS- The authors declare no conflict of interest.
EDAT- 2022/10/15 06:00
MHDA- 2022/10/18 06:00
PMCR- 2022/10/05
CRDT- 2022/10/14 02:12
PHST- 2022/08/11 00:00 [received]
PHST- 2022/09/24 00:00 [revised]
PHST- 2022/09/30 00:00 [accepted]
PHST- 2022/10/14 02:12 [entrez]
PHST- 2022/10/15 06:00 [pubmed]
PHST- 2022/10/18 06:00 [medline]
PHST- 2022/10/05 00:00 [pmc-release]
AID - ijms231911817 [pii]
AID - ijms-23-11817 [pii]
AID - 10.3390/ijms231911817 [doi]
PST - epublish
SO  - Int J Mol Sci. 2022 Oct 5;23(19):11817. doi: 10.3390/ijms231911817.