Differential Effect of Molecular Weight Hyaluronan on Mechanical Stress-induced Inflammatory Response in Human Ligamentum Flavum Fibroblasts

• Main Authors: Chia-Lin Liu, 劉家麟
• Other Authors: Ming-Hong Chen
• Format: Others
• Language: en_US
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/43070141359827705570

碩士 === 國立陽明大學 === 醫學工程研究所 === 99 === Ligamentum flavum hypertrophy contributes to the development of spinal stenosis which comprises narrowing of the spinal canal with subsequent neural compression, and is frequently associated with symptoms of neurogenic claudication. Mechanical stress-induced inflammatory reaction and scar formation have been proposed to constitute an important pathogenetic component in ligamentum flavum hypertrophy. Hyaluronan (HA) has been identified as an important regulator in inflammatory processes and used as an anti-arthritic agent in patients with osteoarthritis and rheumatoid arthritis. Besides chondroprotective effect, interactions between HA and ligamentum flavum flibroblast are attracting interest. The study aims to investigate the differential effect of molecular weight HAs on mechanical stress-induced inflammatory response in ligamentum flavum fibroblasts. We compared the effects of five different molecular weight HAs (40kDa-1700kDa) on centrifugal force induced-inflammatory response in ligamentum flavum fibroblasts from six patients undergoing lumbar spine surgery. Cell viability and cytotoxicity were assayed by colorimetric MTT and lactate dehydrogenase (LDH) Assay, respectively. Specific gene expressions were determined by real-time PCR and doses of prostaglandin E2 (PGE2) and nitric oxide (NO) were measured in the culture supernatants. MAPK family (JNK, ERK and p38 MAPK) were determined by Western blotting analysis. It was found that HA with 900k, 1390k and 1700kDa significantly decreased mechanical stress-induces PGE2 and NO release. 1700kDa HA down regulate stress-induced IL-1α, IL-1β and TNF-α gene expression. High molecular weight HA in our study reveals a better anti-inflammatory effect than low molecular weight HA. The study provides a possible therapeutic strategy for ligamentum flavum hypertrophy.