The Role of Synovial Membrane in the Development of a Potential In Vitro Model of Osteoarthritis

Abstract

There is a lack of in vitro models able to plausibly represent the inflammation microenvironment of knee osteoarthritis (OA). We analyzed the molecules released from OA tissues (synovial membrane, cartilage, infrapatellar fat pad) and investigated whether the stimulation of human synovial fibroblasts (SFs), with synthetic cytokines (IL-1β and TNF-α or IFN-γ) or conditioned media (CM) from OA tissues, influence the SFs’ response, in the sense of pro-inflammatory cytokines, chemokines, growth factors, and degradative enzymes modulation. Human SFs were obtained from OA synovial membranes. SFs and their CM were analyzed for biomarkers, proliferation rate, protein profile and gene expression, before and after stimulation. Real-time PCR and multiplex assays quantified OA-related gene expression and biomolecule production. Unlike other activators, CM from OA synovial membrane (CM-SM), significantly up-regulated all genes of interest (IL-6, IL-8, MMP-1, MMP-3, RANTES, MCP-1, TSG-6, YKL-40) in SFs. Multiplex immunoassay analysis showed that levels of OA-related cytokines (IL-6, IL-8, MCP 1, IL-1Ra), chemokine (RANTES) and growth factor (VEGF), produced by CM-SM stimulated SFs, increased significantly compared to non-stimulated SFs. Molecules released from the SM from OA patients induces OA-like changes in vitro, in specific OA synovial populations (SFs). These findings promote the use and establish a compelling in vitro model that simulates the versatility and complexity of the OA disease. This model, in the future, will allow us to study new cell therapies or test drugs by reducing or avoiding animal models.

Trends in Serum Cytokine Expression in Pediatric Skeletal Dysplasia

“…( 15 ) RANTES (upregulated in eight cohorts) has been identified as a likely factor in the development of osteoarthritis. ( 16 ) IP‐10 (upregulated in eight cohorts) has been negatively correlated with bone mineral density in patients with dermatomyositis. ( 17 ) The majority of identified cytokines are recognized to have some relationship to the musculoskeletal system, albeit in signaling pathways which are early in their elucidation stage.…”

Morphological Comparison of the Stromal-Vascular Fraction of the Subcutaneous Fat Cell and Infrapatellar Fat Pad

“…Літературні джерела свідчать, що мезенхімальні стовбурові клітини, отримані зі синовіальної оболонки, походять із цих периваскулярних клітин. Існує думка, що синовіальна оболонка відіграє активну роль в імуномодуляції колінного суглоба, особливо в разі остеоартриту [18]. Користь клітин синовіальної оболонки відповідає теорії Каплана про те, що МСК працюють за рахунок фактора росту та секреції цитокінів, а не приживлення та диференціювання [19].…”