PMID- 15597148 OWN - NLM STAT- MEDLINE DCOM- 20050324 LR - 20181201 IS - 1023-3830 (Print) IS - 1023-3830 (Linking) VI - 53 IP - 10 DP - 2004 Oct TI - Hyaluronan enhances cartilage repair through low grade tissue remodeling involving cytokines and matrix metalloproteinases. PG - 534-43 AB - OBJECTIVE AND DESIGN: To determine whether the ability of high molecular weight hyaluronan (HA) to reverse cartilage damage caused by specific catabolic mediators of cartilage damage, fibronectin fragments (Fn-fs), occurs through a low grade of enhanced catabolic events such as enhanced matrix metalloproteinase (MMP) expression or cytokine activities. MATERIAL: HA from 6.8-kDa to 2 million daltons was studied. TREATMENT: The ability of HA to enhance matrix metalloproteinase-3 (MMP-3) epitopes and cartilage proteoglycan (PG) degradation neoepitopes was tested in bovine cartilage, as well as the ability of recombinant human interleukin-1 receptor antagonist protein (rhIRAP) to reverse PG depletion in cartilage first exposed to Fn-f. RESULTS: All HA forms enhanced MMP-3 epitopes and PG degradation in normal undamaged cartilage and in the case of HA800, the degradation was not sufficient to decrease steady state levels of cartilage PG. When HA800 was added to Fn-f damaged cartilage, restoration of PG occurred, but this was blocked by rhIRAP. CONCLUSIONS: These results collectively suggest that some of the repair activity of HA800 is through proteolytic activity which is not sufficient to decrease matrix PG content, but is nonetheless elevated above levels in cartilage not treated with HA800. FAU - Homandberg, G A AU - Homandberg GA AD - Department of Biochemistry and Molecular Biology, University of North Dakota School of Medicine and Health Sciences, Box 9037, Grand Forks, ND 58202, USA. ghomandb@medicine.nodak.edu FAU - Ummadi, V AU - Ummadi V FAU - Kang, H AU - Kang H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PL - Switzerland TA - Inflamm Res JT - Inflammation research : official journal of the European Histamine Research Society ... [et al.] JID - 9508160 RN - 0 (Culture Media, Conditioned) RN - 0 (Culture Media, Serum-Free) RN - 0 (Cytokines) RN - 0 (Epitopes) RN - 0 (Fibronectins) RN - 0 (IL1RN protein, human) RN - 0 (Interleukin 1 Receptor Antagonist Protein) RN - 0 (Oligopeptides) RN - 0 (Peptide Fragments) RN - 0 (Prostaglandins) RN - 0 (Recombinant Proteins) RN - 0 (Sialoglycoproteins) RN - 0 (peptide VDIPEN) RN - 67763-96-6 (Insulin-Like Growth Factor I) RN - 9004-61-9 (Hyaluronic Acid) RN - EC 3.4.- (Endopeptidases) RN - EC 3.4.24.- (Matrix Metalloproteinases) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) RN - EC 3.4.99.- (aggrecanase) RN - J2VZ07J96K (Polymyxin B) SB - IM MH - Animals MH - Blotting, Western MH - Cartilage/*drug effects/metabolism MH - Cattle MH - Culture Media, Conditioned/pharmacology MH - Culture Media, Serum-Free/metabolism MH - Cytokines/*metabolism MH - Endopeptidases/chemistry MH - Epitopes/chemistry MH - Fibronectins/chemistry/metabolism MH - Humans MH - Hyaluronic Acid/*chemistry/*pharmacology MH - Immunohistochemistry MH - Insulin-Like Growth Factor I/metabolism MH - Interleukin 1 Receptor Antagonist Protein MH - Kinetics MH - Matrix Metalloproteinase 3/chemistry MH - Matrix Metalloproteinases/*metabolism MH - Oligopeptides/chemistry MH - Peptide Fragments/chemistry MH - Polymyxin B/chemistry MH - Prostaglandins/metabolism MH - Recombinant Proteins/chemistry MH - Sialoglycoproteins/chemistry MH - Time Factors EDAT- 2004/12/15 09:00 MHDA- 2005/03/25 09:00 CRDT- 2004/12/15 09:00 PHST- 2004/12/15 09:00 [pubmed] PHST- 2005/03/25 09:00 [medline] PHST- 2004/12/15 09:00 [entrez] AID - 10.1007/s00011-004-1292-y [doi] PST - ppublish SO - Inflamm Res. 2004 Oct;53(10):534-43. doi: 10.1007/s00011-004-1292-y.