The aseptic loosening of artificial joints with associated periprosthetic bone resorption may be partly due to the suppression of osteoblast function to form new bone by wear debris derived from the joint. To assess the effect of wear debris on osteoblasts, we cultured normal human osteoblasts (NHOst) in contact with several kinds of microspheres as models of wear debris. The NHOst in contact with polystyrene, polyethylene, and alumina microspheres showed a lower differentiation level than NHOst alone as estimated from the amounts of deposited calcium. On the other hand, hydroxyapatite particles enhanced the differentiation of NHOst. In addition, sintered hydroxyapatite enhanced expression of osteocalcin mRNA and gap junctional communication of NHOst. This study suggests that polystyrene, polyethylene, and alumina microspheres have the potential to disorder not only the differentiation but also the homeostasis of NHOst in contact with them. However, hydroxyapatite enhanced the differentiation as well as the homeostasis of NHOst, even in microsphere form, suggesting its good biocompatibility as biomaterials for bone tissues.