Abstract

Autologous conditioned serum (ACS) and autologous protein solution (APS) are newer therapeutic options for osteoarthritis (OA). Co-culture of cartilage and synovium stimulated with IL-1β produces a similar physiologic response to tissues from naturally-ocurring OA. The study objective was to investigate the effects of ACS, APS, and triamcinolone (TA) on inflammatory and catabolic gene expression of inflamed joint tissues in co-culture. Blood was collected and processed for ACS and APS from six horses. Cartilage and synovial explants were harvested from the stifle, placed in co-culture, and treated as: (1) unstimulated control (2) stimulated control (3) ACS at 25% v/v (4) ACS at 50% v/v (5) APS at 25% v/v (6) APS at 50% v/v, (7) TA (10−6 M). Treatment groups 2–7 were stimulated with IL-1β (10 ng/ml). Cultures were maintained for 96 hours, and then both media and explants were harvested for measurement of gene expression and protein. IL-1β stimulation significantly increased IL-1β (p = 0.029), IL-8 (p = 0.011) and MMP-3 (p = 0.043) expression in synovium and IL-1β (p = 0.003) and TNF-α (p = 0.001) expression in cartilage. Treatment with 50% ACS and APS v/v downregulated IL-1β expression in cartilage more than TA treatment (p = 0.001 and p = 0.0004) and APS downregulated MMP-1 expression in synovial membrane (p = 0.025). Treatment with ACS and APS caused a trend in upregulation of IL-10 expression in synovium and type II collagen and aggrecan expression in cartilage. PGE2 media concentrations were significantly reduced following treatment with APS (13.7-fold decrease, p = 0.0001) and ACS (4.13-fold decrease, p = 0.024); while TA did not reduce PGE2 significantly (2.3-fold decreased p = 0.406). As disease-modifying therapies, ACS and APS modified the cellular response from synovial membrane and articular cartilage. ACS and APS may offer an improved strategy to improve clinical signs of horses with naturally occurring OA, compared to TA treatment.

Highlights

  • Lameness due to osteoarthritis (OA) is a leading cause of reduced or lost performance in horses, placing a significant economic hardship on the equine industry [1, 2]

  • Autologous conditioned serum (ACS) had significantly lower red blood cells (RBCs) (p = 0.001), and lower, but no significantly lower white blood cells (WBCs) and PLT counts compared to blood (p = 0.2803 and p = 0.140)

  • When the ratio of IL-1rap: IL-1β ratio was evaluated for each individual horse, ACS (113.31 ± 78.98) had a higher ratio compared to autologous protein solution (APS) (48.22 ± 78.98), but this difference was not significant (p = 0.401)

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Summary

Introduction

Lameness due to osteoarthritis (OA) is a leading cause of reduced or lost performance in horses, placing a significant economic hardship on the equine industry [1, 2]. The mainstay of intra-articular OA therapy is modifying the symptoms of disease through temporary reduction of inflammation via administration of corticosteroids with or without viscosupplementation [4]. Several blood-derived orthobiologic products targeted at disease modification, such as autologous conditioned serum (ACS) and autologous protein solution (APS), are expanding the therapeutic options for clinicians treating horses with joint-related injury. Both products are obtained from the patient’s blood and administered directly into the affected joint(s) for the treatment of OA. Only one study has compared the anti-inflammatory cytokine and growth factor concentration in ACS and APS collected from the same horse, finding APS had higher concentrations of TGF-β [11]

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