Osteoarthritis (OA) is a multifactorial disease subjects to different genetic and environmental factors. Most researches focus on the epigenetic alterations including DNA methylation, histone modiﬁcations, alterations in chromatin structure, and microRNA regulations in cartilage. Although early studies show that synovium secretes catabolic enzymes to degrade cartilage matrix, rare studies address the role of synovium in the onset and progression of OA. In addition, it is known that synovium plays a role in cartilage repair. Moreover, treatments for early stage of OA, such as hyaluronan (HA) supplement and platelet-rich plasma (PRP) injection, may ameliorate both synovium and cartilage. There treatments may possible to relief the inflammation of synovium and subsequently improve the symptoms of OA cartilage. Therefore, the better understanding of the interactions between synovium and cartilage, especially the causal relationship, shall benefit OA therapy. In this component project, the following tasks will be finished in 3 year. Year 1: The cartilage, synovium, and synovial fluid will be harvested during total knee replacement from 4 OA patients. The OA-related gene expressions and cytokine productions will be analyzed using real-time PCR, ELISA, and histological examinations. Year 2: Human chondrocytes and synoviocytes will be isolated from articular cartilage and synovium, respectively. These two types of cells will be stimulated with IL-1β and subsequently treated with antioxidants, HA or PRP (provided by component project 2) separately or in a co-culture model to identify the interactions. After that, the organ culture of cartilage and synovium will be tested under the same design. Year 3: Tissue engineering (TE) synovium (provided from component project 4) will be co-cultured with TE cartilage (prepared from component project 3). The characteristics of these two TE constructs will be evaluated based on the findings of year 1 and the interactions between TE synovium and cartilage will be demonstrated based on the results of year 2. The purpose of this study is to clarify the correlation of synovium and cartilage in OA (year 1), the role of synovium in cartilage repair (year 2), and the combination of TE synovium with TE cartilage for articular cartilage regeneration (year 3).
|Effective start/end date||8/1/14 → 7/31/15|
- pro-inflammatory cytokine
- anabolic and catabolic enzyme