Hyaluronan (HA), a large glycosaminoglycan, is a component of the extra-cellular matrix in various tissues. HA is essential for matrix assembly and fluid viscosity in cartilage, but the roles of HA in bone are unclear. Bone resorption associated with inflammation is closely related to prostaglandin E (PGE) synthesis by osteoblasts induced by cytokines such as interleukin-1 (IL-1). In mouse calvarial Cultures, HA inhibited osteoclastic bone resorption and PGE production induced by IL-1. In mouse osteoblasts, HA suppressed IL-1-induced expression of cyclooxygenase(COX)-2 and membrane-bound PGE synthase (mPGES)-1 mRNAs, and PGE(2) production. Matrix metalloproteinases (MMPs), including MMP-2 and MMP-13, were produced by osteoblasts in response to IL-1, and were clearly suppressed by HA. In osteoblasts, HA suppressed the NF kappa B-dependent transcription in a ILICiferase assay. Therefore, HA acts on osteoblasts to Suppress the production Of PGE2 and MMPs, and inhibits bone resorption, suggesting critical roles of HA in pathological bone loss with inflammation. (C) 2009 Elsevier Inc. All rights reserved.