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

Erica J Secor,Mark W Grzanna,Ann M Rashmir-Raven,Carmelita G Frondoza

doi:10.4236/pp.2018.91002

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.

Highlights

Osteoarthritis (OA) is a painful, chronic degenerative disease which affects the quality of life in both man and animals [1]
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 and prostaglandin E-2 (PGE2) in stimulated chondrocytes
This study provides evidence that the inhibition of MCP-1 can be a specific target for therapeutic intervention

Summary

Introduction

Osteoarthritis (OA) is a painful, chronic degenerative disease which affects the quality of life in both man and animals [1]. OA is characterized by cartilage breakdown, bone remodeling, osteophyte formation and joint inflammation Humans and animals such as horses afflicted with OA suffer from debilitating morbidity [2]. Humans and horses have similar joint volume, structure and biomechanical function [5] [6] Their articular cartilage exhibits similar cellular and molecular characteristics [5] [6]. Because of their common structural, functional and cellular characteristics, horses have been used as an in vivo model for studying human OA Equine joint tissues such as cartilage and their constituent chondrocytes have been beneficial as models for in vitro studies [7] [8] [9] [10] [11]

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