Chondrocyte Production of Pro-Inflammatory Chemokine MCP-1 (CCL-2) and Prostaglandin E-2 Is Inhibited by Avocado/Soybean Unsaponifiables, Glucosamine, Chondroitin Sulfate Combination

Abstract

Osteoarthritis (OA) is a chronic, painful disease affecting articulating joints in man and animals. It is characterized by cartilage breakdown, bone remodeling, osteophyte formation and joint inflammation. Currently used non-steroidal anti-inflammatory drugs for the management of OA are known to have deleterious side effects. To address the need for alternatives, we evaluated the anti-inflammatory effects of a combination of avocado/soybean unsaponifiables (ASU), glucosamine (GLU) and chondroitin sulfate (CS) by measuring chemokine MCP-1 (monocyte chemoattractant protein 1, CCL2) and prostaglandin E-2 (PGE2) in stimulated chondrocytes. As the only cellular constituents of cartilage, chondrocytes are the source of pro-inflammatory mediators that play critical roles in the pathogenesis of OA. Chondrocytes were incubated: with: 1) control media, 2) [ASU + GLU + CS] combination, or 3) Phenylbutazone (PBZ) for 24 hours. Cells were next stimulated with IL-1β or LPS for another 24 hrs. MCP-1 and PGE2 from supernatants were quantitated by immunoassay. Another set of chondrocytes seeded in chamber slides were stimulated with IL-1β for 1 hour and then immunostained for NF-κB. Chondrocytes stimulated with IL-1β or LPS significantly increased MCP-1 and PGE2 production which were significantly reduced after treatment with [ASU + GLU + CS]. In contrast, PBZ significantly reduced PGE2 but not MCP-1 production. IL-1β stimulation induced nuclear translocation of NF-κB, which was inhibited by pre-treatment with either [ASU + GLU + CS] or PBZ. The present study provides evidence that the production of MCP-1 by chondrocytes can be inhibited by the combination of [ASU + GLU + CS] but not by PBZ. In contrast, PGE2 production was inhibited by either treatment suggesting that the production of MCP-1 and PGE2 could be independently regulated. The finding of distinct effects of [ASU + GLU + CS] on MCP-1 and PGE2 synthesis supports a scientific rationale for a multimodal treatment approach in the management of OA.