The role of mesenchymal stem cells in the pathogenesis of Co–Cr–Mo particle induced aseptic loosening: An in vitro study

Abstract

Aseptic loosening is the major factor of failed arthroplasty. Among several theories the particle disease theory is commonly accepted. Different studies examined the complex interactions between wear debris and surrounding cells, especially the monocytic and osteoblastic lineage. This study was designed to elucidate the impact of cobalt–chromium–molybdenum (Co–Cr–Mo) particles on the osteoblastic differentiation and proliferation of human mesenchymal stem cells (hMSC), with respect to the disease pattern of aseptic loosening. The hMSC were incubated in the presence of Co–Cr–Mo particles in different concentrations under growth and osteoinductive conditions. Obtained cultures were analyzed, with respect to cell density and proliferation, using CASY cell count system and Ki-67 immunostaining. Osteogenic differentiation was analyzed by fluorescence microscopy using antibodies for collagen I, alcaline phosphatase, osteocalcin and osteopontin. Additionally, scanning electron microscopy was used to analyze the localisation of Co–Cr–Mo particles in the culture system. Our findings indicate that these particles were located within the hMSC. Proliferation, as well as cell density, was diminished. The remaining cells showed increased staining of osteocalcin and osteopontin, with visible differences in deposition of these proteins, indicating a deregulation of matrix formation and differentiation respectively. Therefore, it is likely that this influence of Co–Cr–Mo particles on hMSC are involved in the disease pattern of aseptic loosening.