VCAM-1 might be a potential angiogenic biomarker for Metal-on-Metal prosthetic device and FSH-induced inflammation

Abstract

Abstract Follicle stimulating hormone (FSH) rises in peri-menopausal women and remains elevated during menopause. Bone loss, previously attributed to estrogen, may be due to direct effect of FSH. On this background of decorticated bone, hips are replaced due to fractures or osteoarthritis. Metal-on-metal (MoM) hips replacements were developed as they were thought to be longer lasting and robust implants. However, in women, they are failing at a significantly higher rate when compared to men. Failure modes include pain, device loosening due to osteolysis and exuberant blood vessel formation resulting in pseudotumor formation. Recent work from our lab has demonstrated the molecular interaction of the wear particles from MoM with immune cells and the release of inflammatory and pro-angiographic factors such as IL-1b, TNF-a and IL-8. Therefore we hypothesize that binding of monocytes to the endothelium induced via FSH and MoM wear particles should stimulate angiogenesis that would increase detectable inflammatory biomarkers. Vascular inflammatory markers were investigated with FSH and MoM particle stimulation of endothelial cells and bound monocytes. From these data, soluble VCAM-1 protein levels increased during monocyte-endothelial co-culture induced by FSH and MoM wear particle co-stimulation. FSH stimulation was also associated with increased monocyte binding and endothelial tube thickness. These data indicate that FSH promotes vascular endothelial cell cohesion and monocyte recruitment, which may lead to increased VCAM-1 expression towards combined MoM wear particle and FSH stimulation. Our findings suggest that sVCAM-1 may be a biomarker of pseudotumor formation elicited by MoM wear particles in women with elevated FSH.