PMID- 14703002
OWN - NLM
STAT- MEDLINE
DCOM- 20040810
LR  - 20191108
IS  - 1594-0667 (Print)
IS  - 1594-0667 (Linking)
VI  - 15
IP  - 5
DP  - 2003 Oct
TI  - The pathophysiology of osteoarthritis.
PG  - 364-72
AB  - Osteoarthritis (OA) is a complex disease whose pathogenesis includes the 
      contribution of biomechanical and metabolic factors which, altering the tissue 
      homeostasis of articular cartilage and subchondral bone, determine the 
      predominance of destructive over productive processes. A key role in the 
      pathophysiology of articular cartilage is played by cell/extra-cellular matrix 
      (ECM) interactions, which are mediated by cell surface integrins. In a 
      physiologic setting, integrins modulate cell/ECM signaling, essential for 
      regulating growth and differentiation and maintaining cartilage homeostasis. 
      During OA, abnormal integrin expression alters cell/ECM signaling and modifies 
      chondrocyte synthesis, with the following imbalance of destructive cytokines over 
      regulatory factors. IL-1, TNF-alpha and other pro-catabolic cytokines activate 
      the enzymatic degradation of cartilage matrix and are not counterbalanced by 
      adequate synthesis of inhibitors. The main enzymes involved in ECM breakdown are 
      metalloproteinases (MMPs), which are sequentially activated by an amplifying 
      cascade. MMP activity is partially inhibited by the tissue inhibitors of MMPs 
      (TIMPs), whose synthesis is low compared with MMP production in OA cartilage. 
      Intriguing is the role of growth factors such as TGF-beta, IFG, BMP, NGF, and 
      others, which do not simply repair the tissue damage induced by catabolic 
      factors, but play an important role in OA pathogenesis.
FAU - Iannone, Florenzo
AU  - Iannone F
AD  - Division of Rheumatology, DIMIMP, University of Bari, Bari, Italy.
FAU - Lapadula, Giovanni
AU  - Lapadula G
LA  - eng
PT  - Journal Article
PT  - Review
PL  - Germany
TA  - Aging Clin Exp Res
JT  - Aging clinical and experimental research
JID - 101132995
SB  - IM
MH  - *Aging
MH  - Humans
MH  - Osteoarthritis/metabolism/pathology/*physiopathology
RF  - 89
EDAT- 2004/01/02 05:00
MHDA- 2004/08/11 05:00
CRDT- 2004/01/02 05:00
PHST- 2004/01/02 05:00 [pubmed]
PHST- 2004/08/11 05:00 [medline]
PHST- 2004/01/02 05:00 [entrez]
AID - 10.1007/BF03327357 [doi]
PST - ppublish
SO  - Aging Clin Exp Res. 2003 Oct;15(5):364-72. doi: 10.1007/BF03327357.