R4303

Molecular Pathogenesis of Bone Degenerative Disease and Associated Inflammatory Processes

Priya Joshi, Maryanne Amour, Fakiha Siddiqui, Jeffrey Liles, Debra Hoppensteadt, Jawed Fareed, William Hopkinson
Loyola University Medical Center

Introduction

Osteoarthritis is one of the most common forms of arthritis, which is a result of the degeneration of protective cartilage at the end of bones, resulting in friction in the joints. This is due to a complex pathophysiologic process where inflammation and physical alterations of the bone contribute to the overall pathology. During this process, several mediators of inflammation and matrix degradation are formed. Profiling of some of these mediators and related biomarkers provides a molecular approach to understand the processes involved in the progression of this disease. The aim of this study is to profile various biomarkers of inflammation and hemostatic activation in osteoarthritis patients undergoing total joint replacement.

Materials and Method

Seventy-four EDTA plasma samples were collected from osteoarthritis patients prior to their surgery. The control comprised of a pool prepared from normal male and female EDTA plasma. Such coagulation markers as D-Dimer, vWF, MP-TF, PAI-1, TAFI, and fibronectin were performed using ELISA techniques. Matrix metallopeptidase 9 (MMP-9) and C-reactive protein were also measured using ELISA methods. All results were compiled as group means and compared with EDTA controls. Appropriate statistical methods were used to analyze the data.

Results

The circulating level of D-Dimer was much higher on average in the patient samples (9178 + 3.56 ng/ml) in comparison to the control samples (115 + 85 ng/ml) p<0.05. The concentration of vWF was higher (125 + 28 %) than in the control sample (104 + 7.4%) p<0.05. There was not a significant difference between the MP-TF or TAFI concentrations in the total joint samples vs the controls p<0.05. There was no correlation among any of the tested biomarkers. 

Conclusion

This data shows that osteoarthritis patients exhibit marked elevation of inflammatory and hemostatic activation biomarkers. Wide variations are noted in the circulating level of these biomarkers in patients. This data suggests that multifactorial processes are involved in the pathogenesis of osteoarthritis. Profiling of inflammatory and thrombotic biomarkers may be helpful in the risk stratification and risk management in these patients.