443 Generation of Osteoarthritis-Like Cytokine Profiles Using an in Vitro Co-Culture Model

DiBenedetto, P.; DiMicco, Michael A.; Chen, F.; Yu, Qilin; Matthews, Geoffrey M.

doi:10.1016/s1063-4584(08)60484-7

Cited by 1 publication

(2 citation statements)

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“…It has been previously established that stem cell pellets will form a chondrogenic pellet with extracellular matrix containing aggrecan and collagen type II within two weeks [48]. It has also been shown by Chen et al [19], Scott et al [45], and DiBenedetto et al [46] that the culture of synovial fibroblasts with U937 cells will produce proinflammatory cytokines and MMPs. This it can be hypothesized that similar results to those shown here could be attained using multiple donors for the stem cells and synovial fibroblasts.…”

Section: Discussionmentioning

confidence: 99%

“…In previous work, contact between the synovium and cartilage components was necessary to initiate GAG loss [45]. A similar coculture model was shown to degrade a cartilage explant in the presence of the catabolic stimulant, fibronectin fragment [46]. In that model, the cocultured synovial fibroblasts and U937 cells were separated from the explants and did not degrade the cartilage significantly without the addition of fibronectin fragment.…”

Section: Discussionmentioning

confidence: 99%

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The degradation of chondrogenic pellets using cocultures of synovial fibroblasts and U937 cells

Blasioli

Matthews²,

Kaplan

2014

Biomaterials

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Osteoarthritis (OA) of the knee is often characterized by joint space narrowing on X-ray, knee pain, and a loss of joint function through progressive cartilage degradation and intermittent synovial inflammation. The objective of this work was to develop an in vitro model in a clinically relevant system. Normal human synovial fibroblasts were cultured with U937 cells for 3 days then combined with a chondrogenic stem cell pellet for another 4 days. This culture system mimicked many of the aspects of early stage OA including production of cytokines and degradative enzymes, MMP-1 and MMP-3, resulting in a conditioned medium profile similar to OA synovial fluid. This catabolic environment resulted in the release of glycosaminoglycan (GAG) from the pellet. In a similar manner to early stage OA, the pellet had increased aggrecan and collagen II expression. All of these effects are hallmarks of early stage OA. This relatively simple tissue model containing a 3D cartilage component interacting with synoviocytes and macrophages could be useful to understand early causes and progression of OA. It can be scaled easily thus useful for high throughput screening of disease modifying drugs in a clinically relevant system.

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