Investigation of Cytokine Changes in Osteoarthritic Knee Joint Tissues in Response to Hyperacute Serum Treatment.

Dorottya Kardos,Stefan Nehrer,Zsuzsanna Gyevnár,Tamás Mirkó Paukovits,Krisztián Magos,Melinda Simon,György Béres,Adél Hinsenkamp,Olga Kuten,Tamás Bárdos,Zsombor Lacza,István Hornyák,Kálmán Szenthe,Bence Marschall,Ferenc Bánáti,Gábor Erdélyi,Susan Szathmary

doi:10.3390/cells8080824

Abstract

One option to fight joint degradation and inflammation in osteoarthritis is the injection of activated blood products into the synovial space. It has been demonstrated that hyperacute serum is the most proliferative among plasma products, so we investigated how the cytokine milieu of osteoarthritic knee joint reacts to hyperacute serum treatment in vitro. Cartilage, subchondral bone, and synovial membrane explanted from osteoarthritic knees were stimulated by interleukin-1 beta (IL-1β) and the concentration of 39 biomarkers was measured in the co-culture supernatant after hyperacute serum treatment. The IL-1β stimulation triggered a strong inflammatory response and enhanced the concentrations of matrix metalloproteinase 3 and 13 (MMP-3 and MMP-13), while hyperacute serum treatment reduced inflammation by decreasing the concentrations of IL-1β, tumor necrosis factor alpha (TNF-α), interleukin-6 receptor alpha (IL-6Rα), and by increasing the level of interleukin-1 antagonist (IL-1RA) Cell viability increased by day 5 in the presence of hyperacute serum. The level of MMPs-1, 2, and 9 were higher on day 3, but did not increase further until day 5. The concentrations of collagen 1 alpha 1 (COL1A1) and osteonectin were increased and receptor activator of nuclear factor kappa-B ligand (RANKL) was reduced in response to hyperacute serum. We concluded that hyperacute serum treatment induces cell proliferation of osteoarthritic joint tissues and affects the cytokine milieu towards a less inflamed state.

Highlights

Osteoarthritis (OA) is the most common degenerative joint disorder characterized by cartilage degradation, subchondral bone sclerosis, the formation of osteophytes, and synovial inflammation [1].Bone, cartilage, and synovium communicate via soluble mediators secreted into the synovial fluid, the disease affects the whole joint, despite the traditional view that OA is a cartilage-only disorder [2]
We showed that it is possible to mimic the cytokine milieu of the osteoarthritic knee joint in an in vitro explant co-culture model
All 39 cytokines that were described in the synovial fluid as markers of OA have been promptly generated by this co-culture in a similar concentration as in vivo

Summary

Introduction

Cartilage, and synovium communicate via soluble mediators secreted into the synovial fluid, the disease affects the whole joint, despite the traditional view that OA is a cartilage-only disorder [2] It is unknown yet, whether synovial inflammation is the primary effect of the disease or whether it is the result of the cartilage degradation and subchondral bone lesion [3]. IL-1β and TNF-α induce chondrocyte, synovial, and immune cells to produce a broad spectrum of inflammatory proteins, such as IL-2, IL-6, IL-12, IL-15, IL-17, IL-18, and IL-21 They evoke apoptosis of chondrocytes and synovial fibroblasts and inhibit synthesis of collagen-type II and aggrecan [5].

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