Author(s)

Erica J. Secor¹, Mark W. Grzanna², Ann M. Rashmir-Raven³, Carmelita G. Frondoza^2,4,5*

¹College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
²Department of Research and Development, Nutramax Laboratories Inc., Edgewood, USA.
³College of Veterinary Medicine, Michigan State University, East Lansing, USA.
⁴Department of Orthopedic Surgery, Johns Hopkins University, Baltimore, USA.
⁵College of Veterinary Medicine, Mississippi State University, Starkville, USA.

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.

Inflammation, Chondrocytes, Avocado/Soybean Unsaponifiables, Glucosamine, Chondroitin Sulfate

Secor, E. , Grzanna, M. , Rashmir-Raven, A. and Frondoza, C. (2018) Chondrocyte Production of Pro-Inflammatory Chemokine MCP-1 (CCL-2) and Prostaglandin E-2 Is Inhibited by Avocado/Soybean Unsaponifiables, Glucosamine, Chondroitin Sulfate Combination. Pharmacology & Pharmacy, 9, 10-26. doi: 10.4236/pp.2018.91002.