Anti-inflammatory and Chondro-protective Effects of Different Molecular Weight Hyaluronic Acid on Fibroblast-like Synoviocyte from Patients with Traumatic Arthritis and Osteoarthritis
Date Issued
2010
Date
2010
Author(s)
Huang, Teng-Le
Abstract
Background: Post-traumatic osteoarthritis (OA) is a common sequela in patients following intra-articular fracture, especially in weight-bearing joints. Subsequent reconstructive surgeries may not correct all the problems that relate to patient’s disability. Prevention at the very early stage and changing the nature history of the disease will be the more reasonable and feasible modality of resolution.
Intra-articular injections of hyaluronic acid (HA) into OA joints have been reported to relieve joint pain and improve function, which are now licensed worldwide for the treatment of OA. However, few studies evaluate the feasibility of using HA to prevent OA progression in early stage traumatic arthritis. In addition, previous studies concerning this issue were all conducted in animal models. There is still limited understanding regarding this efficacy in human.
Many investigators have reported that the molecular weight (MW) of HA in diseased joint is much lower than that in normal joint, implying joints with higher MW HA get better function. However, there are three human HA synthase (HAS) genes synthesizing different MW HAs in human synovial joint. HA with higher MW (2 x 106 Da) is synthesized by HAS 1 and HAS 2, whereas HA with lower MW (2-3 x 105 Da) is synthesized by HAS 3. If low MW HA is nothing but a depolymerized product, HAS 3 that synthesizes LMW HA should be deleted during the human evolution process.
Increasing evidences suggest that HA may not only provide an anti-inflammatory effect but also a chondro-protective effect, which modify the progression of OA. Controversy exists concerning whether these effects are molecular weight dependent.
In this thesis, whether HA would induce expression of OA-related factors associated with improved outcomes in patients with tibia plateau fracture was examined in the first part experiments. Besides, the effects of two different MW HAs on six OA-related proteins expressed in fibroblast-like synoviocytes (FLS) from patients with tibia plateau fracture were compared and analyzed in the second part experiments. Furthermore, in the third part experiments, it was hypothesized that HA with different MW may have different contributions in the maintenance of normal joint physiology. The effects of three different MW HAs on seven OA-related proteins expression in FLS from patients with early stage OA were evaluated in this part.
Methods: The interleukin (IL)-1-β induced or un-induced FLS from patients with tibia plateau fracture and early stage OA and were cultivated with or without the treatment of HA. Quantifications of these factors are performed with sandwich Enzyme-Linked Immuno-Sorbent Assay (ELISA) by using commercially available kits.
Results: (1). HA downregulated the expression of catabolic factors, including IL-1, MMP-3, and TNF-α, and upregulated the production of anticatabolic factors such as TIMP-1 and TIMP-2. HA promoted the creation of interleukin-10, an anti-inflammatory cytokine, in FLS. (2). HA with a high MW (HMW) is more effective in down-regulating proinflammatory cytokines such as IL-1β and TNF–
Subjects
arthritis
hyaluronic acid
molecular weight
SDGs
Type
thesis
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