Effect of polymerized-type I collagen in knee osteoarthritis. I. In vitro study.
BACKGROUND
Polymerized-type I collagen (polymerized-collagen) is a down-regulator of inflammation and a tissue regenerator biodrug. The aim of this study was to evaluate its effect in co-cultures of cartilage and synovial tissue from patients with knee osteoarthritis (OA).


METHODS
Cartilage and synovial tissue from five patients with OA were co-cultured for 7 days in the presence or absence of 1% polymerized-collagen. To determine proteoglycans content, tissues were stained with alcian blue technique. Pro- and anti-inflammatory cytokines [interleukin (IL)-1beta, IL-8, IL-10, IL-12, tumour necrosis factor (TNF)-alpha, and interferon (IFN)-gamma] and tissue inhibitor of metalloproteinase (TIMP)-1 were measured in supernatants by ELISA and results were normalized by total protein concentration. Cartilage oligomeric matrix protein (COMP), type II collagen, TNF-alpha, IL-10 and Ki-67 expression were determined by immunohistochemistry.


RESULTS
Polymerized-type I collagen induced an increase of 3- to 6fold cell proliferation (Ki-67), proteoglycans content, and COMP and type II collagen expression, whereas it inhibited IL-1beta and TNF-alpha production. IL-10 levels were up-regulated in treated vs. untreated cultures. No differences were found on IL-8 or TIMP-1 levels in supernatants from polymerized-collagen-treated co-cultures when compared with untreated cultures. IL-12 and IFN-gamma were undetectable.


CONCLUSIONS
The addition of polymerized-type I collagen to cartilage and synovial tissue co-cultures induced up-regulation of chondrocytes proliferation and cartilage extracellular matrix proteins production (COMP, type II collagen and proteoglycans) as well as an anti-inflammatory cytokine (IL-10) and the down-modulation of pro-inflammatory cytokines (IL-1beta and TNF-alpha). It is possible that this mechanism might contribute to induce tissue regeneration and down-regulation of inflammation in OA.
Furuzawa-Carballeda
J
J
Department of Immunology and Rheumatology, National Institute of Medical Sciences and Nutrition Salvador Zubirán, Mexico City, Mexico. jfuruzawa@gmail.com
Muñoz-Chablé
O A
OA
Barrios-Payán
J
J
Hernández-Pando
R
R
D000368:Aged; D000369:Aged, 80 and over; D002356:Cartilage / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D024042:Collagen Type I / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D020370:Osteoarthritis, Knee / Q000188:drug therapy / Q000473:pathology*; D013583:Synovial Membrane / Q000473:pathology*
D024042:Collagen Type I