PMID- 25125146 OWN - NLM STAT- MEDLINE DCOM- 20151120 LR - 20211021 IS - 1573-2576 (Electronic) IS - 0360-3997 (Linking) VI - 38 IP - 1 DP - 2015 Feb TI - Relevance of the myeloid differentiation factor 88 (MyD88) on RANKL, OPG, and nod expressions induced by TLR and IL-1R signaling in bone marrow stromal cells. PG - 1-8 LID - 10.1007/s10753-014-0001-4 [doi] AB - The myeloid differentiation factor 88 (MyD88) plays a pivotal role in Toll-like receptor (TLR)- and interleukin-1 receptor (IL-1R)-induced osteoclastogenesis. We examined the role of MyD88 on p38 mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B cell (NF-kappaB) activation and nucleotide-binding oligomerization domain (Nod) induction by lipopolysaccharide (LPS) and IL-1 beta, and their effect on receptor activator of NF-kappaB ligand (RANKL) and osteoprotegerin (OPG) production in bone marrow stromal cell (BMSC). RANKL, Nod1, Nod2, NF-kappaB, and p38 protein levels were determined by Western blot. Nod2 was stimulated with muramyl dipeptide (MDP) prior to TLR4 stimulation with LPS. MyD88 deficiency markedly inhibited RANKL expression after LPS stimulation and increased OPG messenger RNA (mRNA) production. Also, MyD88 was necessary for NF-kappaB and p38 MAPK activation. MDP alone did not induce RANKL and OPG expressions; however, when combined with LPS, their expressions were significantly increased (p < 0.05). Our results support that MyD88 signaling has a pivotal role in osteoclastogenesis thought NF-kappaB and p38 activation. Nod2 and especially Nod1 levels were influenced by MyD88. FAU - Leite, Fabio Renato Manzolli AU - Leite FR AD - School of Dentistry, Federal University at Pelotas (UFPel), Pelotas, RS, Brazil. FAU - de Aquino, Sabrina Garcia AU - de Aquino SG FAU - Guimaraes, Morgana Rodrigues AU - Guimaraes MR FAU - Cirelli, Joni Augusto AU - Cirelli JA FAU - Zamboni, Dario S AU - Zamboni DS FAU - Silva, Joao S AU - Silva JS FAU - Junior, Carlos Rossa AU - Junior CR LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Inflammation JT - Inflammation JID - 7600105 RN - 0 (Myd88 protein, mouse) RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (NOD1 protein, human) RN - 0 (NOD2 protein, human) RN - 0 (Nod1 Signaling Adaptor Protein) RN - 0 (Nod2 Signaling Adaptor Protein) RN - 0 (Osteoprotegerin) RN - 0 (RANK Ligand) RN - 0 (Receptors, Interleukin-1) RN - 0 (TNFRSF11B protein, human) RN - 0 (Tnfsf11 protein, mouse) RN - 0 (Toll-Like Receptors) SB - IM MH - Animals MH - Cells, Cultured MH - Gene Expression Regulation MH - Mesenchymal Stem Cells/*metabolism MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Myeloid Differentiation Factor 88/*biosynthesis MH - Nod1 Signaling Adaptor Protein/biosynthesis MH - Nod2 Signaling Adaptor Protein/biosynthesis MH - Osteoprotegerin/*biosynthesis MH - RANK Ligand/*biosynthesis MH - Receptors, Interleukin-1/*biosynthesis MH - Signal Transduction/physiology MH - Toll-Like Receptors/*biosynthesis EDAT- 2014/08/16 06:00 MHDA- 2015/12/15 06:00 CRDT- 2014/08/16 06:00 PHST- 2014/08/16 06:00 [entrez] PHST- 2014/08/16 06:00 [pubmed] PHST- 2015/12/15 06:00 [medline] AID - 10.1007/s10753-014-0001-4 [doi] PST - ppublish SO - Inflammation. 2015 Feb;38(1):1-8. doi: 10.1007/s10753-014-0001-4.