PMID- 23740407 OWN - NLM STAT- MEDLINE DCOM- 20140609 LR - 20240109 IS - 1791-244X (Electronic) IS - 1107-3756 (Linking) VI - 32 IP - 2 DP - 2013 Aug TI - Lipopolysaccharide (LPS) promotes osteoclast differentiation and activation by enhancing the MAPK pathway and COX-2 expression in RAW264.7 cells. PG - 503-10 LID - 10.3892/ijmm.2013.1406 [doi] AB - Bone degradation is a serious complication of chronic inflammatory diseases such as septic arthritis, osteomyelitis and infected orthopedic implant failure. At present, effective therapeutic treatments for lipopolysaccharide (LPS)-induced bone destruction are limited to antibiotics and surgical repair in chronic inflammatory diseases. The present study aimed to evaluate the mechanism of LPS on osteoclast differentiation and activation. RAW264.7 cells were non-induced, or induced by the receptor activator of nuclear factor-kappaB (RANK) ligand (RANKL) and macrophage-colony stimulating factor (M-CSF), and then treated with LPS. Following treatment, the number of osteoclasts and cell viability were measured. The expression of osteoclast-related genes including tartrate-resistant acid phosphatase (TRAP), matrix metalloproteinase-9 (MMP-9), cathepsin K (CK), carbonic anhydrase II (CAII) and cyclooxygenase-2 (COX-2) was determined by RT-PCR. Protein levels of RANK, tumor necrosis factor receptor-associated factor 6 (TRAF6), COX-2 and mitogen-activated protein kinases (MAPK) were measured using western blotting assays. LPS promoted osteoclast differentiation of RAW264.7 cells and differentiated osteoclasts. LPS significantly increased mRNA expression of osteoclast-related genes in RAW264.7 cells. Differentiated osteoclasts were treated with LPS (100 ng/ml) and the results showed a significantly increased mRNA expression of osteoclast-related genes and protein levels of RANK, TRAF6 and COX-2. Furthermore, LPS at 100 ng/ml significantly promoted the MAPK pathway including increasing the phosphorylation of c-Jun N-terminal kinases (JNK) and the phosphorylation of the extracellular signal-regulated kinase (ERK1/2). In conclusion, LPS promoted osteoclast differentiation and activation by enhancing RANK signaling and COX-2 expression. LPS also promoted osteoclast differentiation via activation of the JNK and ERK1/2 cell proliferation pathways. FAU - Hou, Guo-Qing AU - Hou GQ AD - First Affiliated Hospital, Medical College of Shantou University, Shantou, Guangdong 515041, P.R. China. FAU - Guo, Chun AU - Guo C FAU - Song, Guo-Hua AU - Song GH FAU - Fang, Na AU - Fang N FAU - Fan, Wen-Juan AU - Fan WJ FAU - Chen, Xu-Dong AU - Chen XD FAU - Yuan, Lei AU - Yuan L FAU - Wang, Zhen-Quan AU - Wang ZQ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130605 PL - Greece TA - Int J Mol Med JT - International journal of molecular medicine JID - 9810955 RN - 0 (Lipopolysaccharides) RN - 0 (Receptor Activator of Nuclear Factor-kappa B) RN - 0 (TNF Receptor-Associated Factor 6) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) SB - IM MH - Animals MH - *Cell Differentiation MH - Cell Line MH - Cell Survival/drug effects MH - Cyclooxygenase 2/genetics/*metabolism MH - Enzyme Activation/drug effects MH - Gene Expression Regulation/drug effects MH - Lipopolysaccharides/immunology/pharmacology MH - Mice MH - Mitogen-Activated Protein Kinases/*metabolism MH - Osteoclasts/cytology/immunology/*metabolism MH - Phosphorylation MH - Receptor Activator of Nuclear Factor-kappa B/metabolism MH - *Signal Transduction/drug effects MH - TNF Receptor-Associated Factor 6/metabolism EDAT- 2013/06/07 06:00 MHDA- 2014/06/10 06:00 CRDT- 2013/06/07 06:00 PHST- 2013/03/17 00:00 [received] PHST- 2013/05/29 00:00 [accepted] PHST- 2013/06/07 06:00 [entrez] PHST- 2013/06/07 06:00 [pubmed] PHST- 2014/06/10 06:00 [medline] AID - 10.3892/ijmm.2013.1406 [doi] PST - ppublish SO - Int J Mol Med. 2013 Aug;32(2):503-10. doi: 10.3892/ijmm.2013.1406. Epub 2013 Jun 5.