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.