Inflammation　is　a　common　situation　during　bone　healing　and　is　recognized　to　inhibit　osteogenic　differentiation　and　bone　formation.　However,　the　effect　of　inflammation　on　BMP-9-induced　osteoblastic　differentiation　remains　unclear.　In　the　present　study,　we　found　that　an　inflammatory　environment　triggered　by　lipopolysaccharide　(LPS)　in　vitro　suppressed　BMP-9-induced　osteogenic　differentiation.　In　addition,　LPS　decreased　BMP-9-induced　phosphorylation　of　Smad1/5/8　and　showed　obvious　inhibitory　effects　on　BMP-9-induced　Smad　signaling.　We　then　confirmed　that　LPS　and　BMP-9　can　activate　p38MAPK　and　ERK1/2　signaling,　and　that　LPS　stimulation　reduces　BMP-9-induced　Runx2　expression　through　the　activation　of　p38MAPK　and　ERK1/2　signaling.　Finally,　we　determined　that　blockade　of　MAPK　signaling　by　specific　inhibitors　reverses　the　inhibitory　effect　of　LPS　on　BMP-9-induced　osteogenic　differentiation,　and　that　MAPK　acts　as　a　mediator　of　the　negative　regulatory　role　of　LPS　in　BMP-9-induced　activation　of　Smad　signaling.　Based　on　these　results,　we　conclude　that　the　LPS-mediated　inflammatory　environment　inhibits　BMP-9-induced　osteogenic　differentiation,　via　crosstalk　between　BMP/MAPK　and　Smad　signaling.　The　elucidation　of　these　mechanisms　may　hasten　the　development　of　new　strategies　and　improve　the　osteoinductive　efficacy　of　BMP-9　in　the　clinic,　resulting　in　enhanced　osteoblastic　differentiation　and　bone　formation.　(C)　2016　Elsevier　Inc.　All　rights　reserved.