title: Hyaluronan regulates PPARγ and inflammatory responses in IL-1β-stimulated human chondrosarcoma cells, a model for osteoarthritis.
abstract: The carbohydrate polymer, hyaluronan, is a major component of the extracellular matrix in animal tissues. Exogenous hyaluronan has been used to treat osteoarthritis (OA), a degenerative joint disease involving inflammatory changes. The underlying mechanisms of hyaluronan in OA are not fully understood. Pro-inflammatory interleukin (IL)-1β downregulates peroxisome proliferator-activated receptor gamma (PPARγ), and increases expression of matrix metalloproteinases (MMPs) which are responsible for the degeneration of articular cartilage. The effects of low- and high-molecular-weight hyaluronan (oligo-HA and HMW-HA) on the inflammatory genes were determined in human SW-1353 chondrosarcoma cells. HMW-HA antagonized the effects of IL-1β by increasing PPARγ and decreasing cyclooxygenase (COX)-2, MMP-1, and MMP-13 levels. It promoted Akt, but suppressed mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NFκB) signaling, indicating anti-inflammatory effects. In contrast, the cells had overall opposite responses to oligo-HA. In conclusion, HMW-HA and oligo-HA exerted differential inflammatory responses via PPARγ in IL-1β-treated chondrosarcoma cells.
authors: Division of Rheumatology, Immunology, and Allergy, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan.
authors: Chi-Ching
authors: CC
authors: Chang
authors: Ming-Shium
authors: MS
authors: Hsieh
authors: Say-Tsung
authors: ST
authors: Liao
authors: Yi-Hsuan
authors: YH
authors: Chen
authors: Chao-Wen
authors: CW
authors: Cheng
authors: Pai-Tsang
authors: PT
authors: Huang
authors: Yung-Feng
authors: YF
authors: Lin
authors: Chien-Ho
authors: CH
authors: Chen
mesh_terms: D001859:Bone Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D002813:Chondrosarcoma / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry / Q000494:pharmacology*; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000009:adverse effects / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D008962:Models, Theoretical; D008970:Molecular Weight; D010003:Osteoarthritis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D047495:PPAR gamma / Q000235:genetics* / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D047495:PPAR gamma; D006820:Hyaluronic Acid; D020928:Mitogen-Activated Protein Kinases