The following is a summary of the “Direct comparison of non-osteoarthritic and osteoarthritic synovial fluid-induced intracellular chondrocyte signaling and phenotype changes,” published in the January 2023 issue of Osteoarthritis and Cartilage by Housmans, et al.

Researchers sought to compare the essential chondrocyte signaling signatures of synovial fluid from knees without osteoarthritis to that from knees with advanced osteoarthritis because of the crucial role synovial fluid plays in maintaining the microenvironment of the joint and the homeostasis of its associated tissues. In addition, the phenotypic impact of the various signaling pathways on articular chondrocytes was also analyzed.

Antibody arrays were used to analyze the synovial fluid for proteins. Investigators used luciferase-based transcription factor activity assays, real-time quantitative polymerase chain reaction (RT-qPCR), and a phospho-kinase array to examine the effects of synovial fluid from both non-osteoarthritic and arthritic joints on chondrocyte signaling and phenotypic changes.

The origin of osteoarthritic synovial fluid signaling was evaluated by contrasting the signaling responses of conditioned media from cartilage, synovium, infrapatellar fat pad, and meniscus. Drugs that block the effects of synovial fluid from osteoarthritis were used to examine the pathways that lead to the disease’s characteristic symptoms. The osteoarthritic synovial fluid contained more cytokines, chemokines, and growth factors than normal synovial fluid, which led to different MAPK, AKT, NFκB, and cell cycle signaling in chondrocytes. By analyzing functional pathways, the study group found that stimulation of synovial fluid in people with osteoarthritis triggered an increase in the activity of these signaling events. 

Tissue secretomes from arthritic cartilage, synovium, infrapatellar fat pad, and meniscus triggered multiple inflammatory signaling pathways. Additionally, the osteoarthritic synovial fluid’s unique pathway signatures accelerated chondrocyte dedifferentiation via MAPK/ERK signaling, increased chondrocyte fibrosis via MAPK/JNK and PI3K/AKT activation, induced an elevated inflammatory response via cPKC/NFκB, facilitated the production of extracellular matrix-degrading enzymes via MAPK/p3 and PI3K/AKT routes, and enabled

This is the first study to directly compare the synovial fluid of people without OA to those with the condition, and the results highlight the importance of MAPKs, cPKC/NFκB, and PI3K/AKT as key intracellular signaling routes associated with OA.