involvement of tolllike receptor 2 and proapoptotic signaling pathways in bone remodeling in osteomyelitis background and aims osteomyelitis is a common manifestation of invasive staphylococcus aureus infection characterized by bone loss and destruction we investigated the role of tolllike receptor 2 tlr2 in bacterial recognition and clearance in response to infection with an osteomyelitis isolate of s aureusmethods apoptosis was assessed in the osteoblastic cell line mc3t3e1 by annexin vfitcpi staining and flow cytometry the expression of tlr2 and apoptosisrelated and mitogenactivated protein kinase pathway proteins was assessed by qrtpcr and western blotting alkaline phosphatase alp activity and calcium deposition were assessed by alp activity assay and alizarin red stainingresults s aureus induced apoptosis upregulated tlr2 expression and activated mitogenactivated protein kinase pathways in a time dependent manner inhibition of the cjun nterminal kinase jnk pathway downregulated tlr2 and suppressed the s aureus induced activation of proapoptotic pathways shorthairpin rna mediated silencing of tlr2 reversed s aureus induced apoptosis and decrease in alp activity and calcium deposition and inhibition of jnk had a similar effectconclusion we showed that osteoblast apoptosis and osteogenic differentiation in response to bacterial invasion are dependent on tlr2 expression and jnk activation suggesting novel potential therapeutic targets for the treatment of osteomyelitis