Recent epidemiological surveys have revealed that diabetes is a risk factor for bone fracture. The mechanism for this presumably relates to the various factors associated with diabetics (e.g., insulin deficiency or resistance and/or continuous hyperglycemia). We, therefore, studied the effects of high glucose and tumor necrosis factor α(TNFα) on osteoblasts and osteoclasts; TNFα has been shown to be a key factor responsible for insulin resistance. High glucose concentrations (60 mM) did not affect alkaline phosphatase (ALP) activity in mouse primary osteoblasts (OBs), whereas TNFα decreased ALP activity. Treatment of OBs with TNFαshowed an increased number of apoptotic cells. When mouse OBs and bone marrow cells were cultured in the presence of PGE2 and 1,25(OH)2D3, osteoclasts (OCs) were formed under high glucose concentrations (5.6-60 mM), while TNFα inhibited OC formation in the co-cultures. When mature OCs were studied with respect to bone resorbing function, it was found that bone resorption was inhibited by exposure to high glucose (15-60 mM). TNFα also inhibited bone resorbing capacity. The effects of decreased bone resorption were, at least partly, due to the deranged actin ring formation of OCs. Although OC formation and function was modified, these agents did not influence the expression of receptor activator of nuclear factor κB ligand and osteoprotegerin in OBs nor the expression of receptor activator of nuclear factor κ B in OC progenitors. These results indicate that the functions of OBs and OCs could be modified to some extent by TNFα , together with high glucose. This study also supports our recent observation that rats with type 2 diabetes showed low turnover of bone, which resulted in deranged mechanical properties of bone
