PMID- 10943863
OWN - NLM
STAT- MEDLINE
DCOM- 20000907
LR  - 20220227
IS  - 0004-3591 (Print)
IS  - 0004-3591 (Linking)
VI  - 43
IP  - 8
DP  - 2000 Aug
TI  - Human chondrocytes express functional chemokine receptors and release 
      matrix-degrading enzymes in response to C-X-C and C-C chemokines.
PG  - 1734-41
AB  - OBJECTIVE: Human chondrocytes produce different C-X-C and C-C chemokines under 
      basal conditions and upon activation with proinflammatory cytokines. We 
      investigated whether human chondrocytes also have chemokine receptors and 
      examined the effects of chemokines on chondrocyte activity. METHODS: The 
      expression of chemokine receptors was determined by immunochemical analysis of 
      frozen sections from normal and osteoarthritic cartilage and by flow cytometry of 
      isolated cells. The messenger RNA expression for chemokine receptors was studied 
      by reverse transcriptase-polymerase chain reaction. Isolated chondrocytes were 
      stimulated with different chemokines, and the responses were evaluated by 
      assaying the release of matrix metalloprotease 3 (MMP-3) and of the lysosomal 
      enzyme N-acetyl-beta-D-glucosaminidase in the supernatants. RESULTS: A wide 
      variety of chemokine receptors (CCR-1, CCR-2, CCR-3, CCR-5, CXCR-1, and CXCR-2) 
      was detected on human chondrocytes. Interaction of these receptors with the 
      corresponding ligands induced the release of MMP-3. This response was abrogated 
      by pretreatment of the cells with Bordetella pertussis toxin, demonstrating 
      involvement of G proteins of the Gi type. The response decreased in the presence 
      of cycloheximide, indicating dependence on protein synthesis. Chemokines also 
      induced the exocytosis of N-acetyl-beta-D-glucosaminidase, which was prevented by 
      receptor blockage with anti-CCR-3 and by treatment with B pertussis toxin. 
      Chondrocytes obtained from osteoarthritic tissue showed an increased expression 
      of CCR-3 and possibly of CXCR-1, and an augmented release of matrix-degrading 
      enzymes compared with chondrocytes from normal donors. CONCLUSION: Our findings 
      suggest the existence in human chondrocytes of a novel catabolic pathway, primed 
      by chemokines and their receptors, that leads to the breakdown of cartilage 
      matrix components.
FAU - Borzi, R M
AU  - Borzi RM
AD  - Istituti Ortopedici Rizzoli, Bologna, Italy.
FAU - Mazzetti, I
AU  - Mazzetti I
FAU - Cattini, L
AU  - Cattini L
FAU - Uguccioni, M
AU  - Uguccioni M
FAU - Baggiolini, M
AU  - Baggiolini M
FAU - Facchini, A
AU  - Facchini A
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 (Chemokines, CC)
RN  - 0 (Chemokines, CXC)
RN  - 0 (Receptors, Chemokine)
RN  - EC 3.2.1.52 (Acetylglucosaminidase)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Acetylglucosaminidase/metabolism
MH  - Chemokines, CC/*pharmacology
MH  - Chemokines, CXC/*pharmacology
MH  - Chondrocytes/cytology/*metabolism
MH  - Exocytosis
MH  - Humans
MH  - Matrix Metalloproteinase 3/*metabolism
MH  - Receptors, Chemokine/*biosynthesis
EDAT- 2000/08/16 11:00
MHDA- 2000/09/09 11:01
CRDT- 2000/08/16 11:00
PHST- 2000/08/16 11:00 [pubmed]
PHST- 2000/09/09 11:01 [medline]
PHST- 2000/08/16 11:00 [entrez]
AID - 10.1002/1529-0131(200008)43:8<1734::AID-ANR9>3.0.CO;2-B [doi]
PST - ppublish
SO  - Arthritis Rheum. 2000 Aug;43(8):1734-41. doi: 
      10.1002/1529-0131(200008)43:8<1734::AID-ANR9>3.0.CO;2-B.