PMID- 23552998
OWN - NLM
STAT- MEDLINE
DCOM- 20130904
LR  - 20181203
IS  - 1529-0131 (Electronic)
IS  - 0004-3591 (Linking)
VI  - 65
IP  - 7
DP  - 2013 Jul
TI  - Identification of soluble 14-3-3∊ as a novel subchondral bone mediator involved 
      in cartilage degradation in osteoarthritis.
PG  - 1831-42
LID - 10.1002/art.37951 [doi]
AB  - OBJECTIVE: Mechanical stress plays an important role in cartilage degradation and 
      subchondral bone remodeling in osteoarthritis (OA). The remodeling of the 
      subchondral bone could initiate cartilage loss in OA through the interplay of 
      bone and cartilage. The aim of this study was to identify soluble mediators 
      released by loaded osteoblasts/osteocytes that could induce the release of 
      catabolic factors by chondrocytes. METHODS: Murine osteoblasts/osteocytes were 
      subjected to cyclic compression, and then conditioned medium from either 
      compressed (CCM) or uncompressed (UCM) cells was used to stimulate mouse 
      chondrocytes. Chondrocyte expression of matrix metalloproteinase 3 (MMP-3), 
      MMP-13, type II collagen, and aggrecan was assessed by reverse 
      transcription-polymerase chain reaction, Western blotting, and enzyme-linked 
      immunosorbent assay. Soluble mediators released by compressed 
      osteoblasts/osteocytes were identified using iTRAQ (isobaric tags for relative 
      and absolute quantification), a differential secretome analysis. Subchondral bone 
      and cartilage samples were isolated from OA patients, and culture medium 
      conditioned with OA subchondral bone or cartilage was used to stimulate human 
      chondrocytes. RESULTS: Stimulation of mouse chondrocytes with CCM strongly 
      induced the messenger RNA (mRNA) expression and protein release of MMP-3 and 
      MMP-13 and inhibited the mRNA expression of type II collagen and aggrecan. 
      Differential secretome analysis revealed that 10 proteins were up-regulated in 
      compressed osteoblasts/osteocytes. Among them, soluble 14-3-3∊ (s14-3-3∊) 
      dose-dependently induced the release of catabolic factors by chondrocytes, 
      mimicking the effects of cell compression. Addition of a 14-3-3∊ blocking 
      antibody greatly attenuated the CCM-mediated induction of MMP-3 and MMP-13 
      expression. Furthermore, in human OA subchondral bone, s14-3-3∊ was strongly 
      released, and in cultures of human OA chondrocytes, s14-3-3∊ stimulated MMP-3 
      expression. CONCLUSION: The results of this study identify s14-3-3∊ as a novel 
      soluble mediator critical in the communication between subchondral bone and 
      cartilage in OA. Thus, s14-3-3∊ may be a potential target for future therapeutic 
      or prognostic applications in OA.
CI  - Copyright (c) 2013 by the American College of Rheumatology.
FAU - Priam, Sabrina
AU  - Priam S
AD  - University Pierre and Marie Curie Paris VI, Paris, France.
FAU - Bougault, Carole
AU  - Bougault C
FAU - Houard, Xavier
AU  - Houard X
FAU - Gosset, Marjolaine
AU  - Gosset M
FAU - Salvat, Colette
AU  - Salvat C
FAU - Berenbaum, Francis
AU  - Berenbaum F
FAU - Jacques, Claire
AU  - Jacques C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (14-3-3 Proteins)
RN  - 0 (Aggrecans)
RN  - 0 (Collagen Type II)
RN  - EC 3.4.24.- (Matrix Metalloproteinase 13)
RN  - EC 3.4.24.- (Mmp13 protein, mouse)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - EC 3.4.24.17 (Mmp3 protein, mouse)
SB  - IM
MH  - 14-3-3 Proteins/*metabolism
MH  - Aggrecans/metabolism
MH  - Animals
MH  - Bone Remodeling/physiology
MH  - Cartilage, Articular/*metabolism
MH  - Cells, Cultured
MH  - Chondrocytes/*metabolism
MH  - Collagen Type II/metabolism
MH  - Humans
MH  - Matrix Metalloproteinase 13/metabolism
MH  - Matrix Metalloproteinase 3
MH  - Mice
MH  - Osteoarthritis/*metabolism
MH  - Osteoblasts/*metabolism
MH  - Osteocytes/*metabolism
MH  - Stress, Mechanical
EDAT- 2013/04/05 06:00
MHDA- 2013/09/05 06:00
CRDT- 2013/04/05 06:00
PHST- 2012/06/06 00:00 [received]
PHST- 2013/03/19 00:00 [accepted]
PHST- 2013/04/05 06:00 [entrez]
PHST- 2013/04/05 06:00 [pubmed]
PHST- 2013/09/05 06:00 [medline]
AID - 10.1002/art.37951 [doi]
PST - ppublish
SO  - Arthritis Rheum. 2013 Jul;65(7):1831-42. doi: 10.1002/art.37951.