Interleukin-1 and transforming growth factor-beta 1 as crucial factors in osteoarthritic cartilage metabolism.
In osteoarthritis (OA), interleukin-1 (IL-1) stimulates the expression of metalloproteinases and aggrecanases, which induce cartilage degradation. IL-1 is also capable of reducing the production of cartilage-specific macromolecules, including type II collagen, through modulation of the transcription factors Sp1 and Sp3. Conversely, Transforming growth factor-beta (TGF-beta) counteracts with most of the IL-1 deleterious effects and contributes to cartilage homeostasis. However, OA chondrocytes progressively loose the expression of TGF-beta type II receptor and become insensitive to the factor. This downregulation is also driven by IL-1. This review provides insights into the molecular mechanisms that underly the interplay between IL-1 and TGF-beta in OA cartilage metabolism and enlightens the central role of Sp1 and Sp3 transcription factors in the matrix pathological alterations.
Pujol
Jean-Pierre
JP
Laboratory of Connective Tissue Biochemistry, Faculty of Medicine, Caen Cedex, France. jean-pierre.pujol@unicaen.fr
Chadjichristos
Christos
C
Legendre
Florence
F
Bauge
Catherine
C
Beauchef
Gallic
G
Andriamanalijaona
Rina
R
Galera
Philippe
P
Boumediene
Karim
K
D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism*; D019902:Chondrocytes / Q000378:metabolism*; D024043:Collagen Type II / Q000096:biosynthesis; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D010003:Osteoarthritis / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D016329:Sp1 Transcription Factor / Q000378:metabolism; D051705:Sp3 Transcription Factor / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D024043:Collagen Type II; D007375:Interleukin-1; D018125:Receptors, Transforming Growth Factor beta; D016329:Sp1 Transcription Factor; D053773:Transforming Growth Factor beta1; D051705:Sp3 Transcription Factor