Hyaluronan Suppresses IL-1[beta]-induced Metalloproteinase Activity from Synovial Tissue.Waddell, David D MD*; Kolomytkin, Oleg V PhD*; Dunn, Sharon PhD†; Marino, Andrew A PhD*‡Author Information From the Departments of *Orthopaedic Surgery, †Rehabilitation Sciences, and ‡Cellular Biology and Anatomy, LSU Health Sciences Center, Shreveport, LA. Received: December 12, 2006 Revised: May 2, 2007; July 5, 2007; July 27, 2007 Accepted: August 15, 2007 All authors received funding from Genzyme Biosurgery, Ridgefield, NJ. One of the authors (DDW) certifies that he has or may receive payments or benefits from a commercial entity related to this work. Each author certifies that his or her institution has approved the human protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research. Correspondence to: Andrew A. Marino, PhD, Department of Orthopaedic Surgery, LSU Health Sciences Center, PO Box 33932, Shreveport, LA 71130-3932. Phone: 318-675-6180; Fax: 318-675-6186; E-mail: [email protected]. Clinical Orthopaedics and Related Research (1976-2007): December 2007 - Volume 465 - Issue - pp 241-248 doi: 10.1097/BLO.0b013e31815873f9 Buy Metrics Abstract Intraarticular injection of hyaluronan (viscosupplementation) is commonly used to treat knee pain from osteoarthritis. The therapeutic benefit might derive from hyaluronan inhibition of the activity of the cytokine-regulated catabolic enzymes that attack joint cartilage (matrix metalloproteinases). We tested the hypothesis that hyaluronan inhibited interleukin-1β-induced matrix metalloproteinase activity secreted by explants of synovial tissue from patients with osteoarthritis and investigated the mechanism of the effect. Hyaluronan with a molecular mass of 12.8 MDa (number average) antagonized induced metalloproteinase activity in proportion to hyaluronan concentration in the clinically relevant range of 2 to 8 mg/mL. The effect was not attributable solely to molecular mass because 1.2-MDa hyaluronan produced comparable inhibition. Based on measurements involving hyaluronans of different average molecular masses, polydispersity and viscosity were similarly ruled out as primary responsible factors. The effect of hyaluronan on induced metalloproteinase activity was mediated partially by CD44, the principal cell surface receptor for hyaluronan. Hyaluronan inhibited interleukin-1β-induced metalloproteinase production from osteoarthritic synovial tissue by a process that was not solely dependent on hyaluronan molecular mass but that was partly mediated by hyaluronan binding to CD44. The efficacy of viscosupplementation could be explained if hyaluronan also blocked catabolic enzyme activity in the joint. © 2007 Lippincott Williams & Wilkins, Inc.